Hedvig Marie Egeland Nordeng

• Johnson, Hannah; Dolk, Helen; Loane, Maria; Damase-Michel, Christine; Given, Joanne & Nordeng, Hedvig Marie Egeland [Show all 23 contributors for this article] (2026). Case-malformed signal detection and prioritisation using EUROmediCAT data for pharmacovigilance in pregnancy. British Journal of Clinical Pharmacology. ISSN 0306-5251. 92(10), p. 3586–3597. doi: 10.1002/bcp.70645. Full text in Research Archive
• Alcalde-Herraiz, Marta; Du, Mike; Sanchez-Parada, Aina; Duarte-Salles, Talita; Palomar-Cros, Anna & Giuliodori, Agustina [Show all 13 contributors for this article] (2026). The effectiveness of HPV vaccination against invasive cervical cancer and related precancerous lesions: a multinational target trial emulation study. The Lancet Primary Care. 2(3). doi: 10.1016/j.lanprc.2026.100114. Full text in Research Archive Show summary

  Background Human Papillomavirus (HPV) vaccines prevent HPV infection and related disease. 15 years after the first HPV vaccination programmes were launched in Europe, their long-term effectiveness can now start to be assessed. We designed a target trial emulation study to estimate the effectiveness of HPV vaccination in preventing invasive cervical cancer and high-grade precancerous lesions using three primary care databases. Methods In this target trial emulation study, we analysed primary care records from the UK (Clinical Practice Research Datalink; data from Sept 9, 1987 to Dec 15, 2023), primary care records linked to hospital records from Catalonia, Spain (Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primària; Jan 1, 2006 to June 30, 2023), and nationwide linked health registry (including primary care, secondary care, and other health data) in Norway (Norwegian Linked Health Registry; Jan 1, 2018 to Dec 31, 2023), all standardised to the Observational Medical Outcomes Partnership common data model. We included women aged 15 years or younger in 2008, coinciding with the start of public vaccination programmes. Exposure was defined as receiving one or more HPV vaccine doses by age 15 years. The main outcomes included high-grade cervical intraepithelial neoplasia (CIN2+), invasive cervical cancer, and conisation (as a proxy for CIN2+ diagnosis). Vaccinated and unvaccinated cohorts were sequentially matched on an annual basis by year of birth, location, and propensity scores, with up to five vaccinated people matched to an unvaccinated individual. Vaccine effectiveness, based on incidence rate ratios after 15 years of follow-up, were calculated using Poisson regression. Results across databases were meta-analysed using fixed-effects. The specified primary analysis in the original protocol was designed to assess exposure by HPV brand versus unvaccinated populations; however, due to the low number of events by brand, the study was underpowered and the primary analysis was amended to assess HPV vaccination exposure overall (any brand) versus unvaccinated. Findings After two-step matching, our analysis included 81 863 vaccinated and 46 357 unvaccinated women from the UK; 148 214 vaccinated and 39 952 unvaccinated from Spain; and 14 885 vaccinated and 4073 unvaccinated from Norway. Fewer than five cervical cancers were observed per cohort, precluding vaccine effectiveness estimation for this outcome. Meta-analytic vaccine effectiveness at 15 years was 42% (95% CI 6–64) against CIN2+ and 58% (6–82) against conisation. Interpretation Our estimates of vaccine effectiveness against CIN2+ and conisation in Europe align with estimates from previous systematic reviews of randomised controlled trials. We also observed an increased health-seeking behaviour among vaccinated individuals, suggesting that our study might have underestimated vaccine effectiveness. Further studies with longer follow-up are needed to estimate vaccine effectiveness against cervical cancer.

• Carson, Alexis Christine; Zidan, Mahmoud; Olstad, Emilie Willoch; Gervin, Kristina; Galesloot, Tessel E. & Scholte, Iris [Show all 9 contributors for this article] (2026). Genetically Informed Research Designs in Perinatal Pharmacoepidemiology: A Methodological Overview. Drug Safety. ISSN 0114-5916. 49(7), p. 761–773. doi: 10.1007/s40264-026-01647-9. Full text in Research Archive Show summary

  Despite the widespread use of medications during pregnancy, ethical and methodological barriers to clinical trials make observational studies necessary for evaluating medication safety in this population. Observational studies are prone to biases that often limit their validity due to the lack of randomization; integrating genetic information through discordant sibling designs, polygenic scores, and Mendelian randomization can address several confounding issues. However, application of these three approaches in perinatal pharmacoepidemiology has been limited. Complementing traditional designs with these genetically informed research designs can tackle common biases and strengthen causal inference. This paper focuses on applying genetically informed research designs to child outcomes in perinatal pharmacoepidemiology by reviewing various methods, discussing their strengths and limitations, and examining their application to date, as well as considerations for implementing them in future research. Such considerations include the availability of genetic data, the complexity of integrating genetic data with existing epidemiological data, and selection of appropriate genetic instruments for analyses. Incorporating causal inference in perinatal pharmacoepidemiology can ultimately contribute to enhancing safe medication use during pregnancy.

• Limoncella, Giorgio; Girardi, Anna; Bartolini, Claudia; Hyeraci, Giulia; Roberto, Giuseppe & Paoletti, Olga [Show all 48 contributors for this article] (2026). Identifying Pregnancies in Population-Based Data Sources: Development and Application of the ConcePTION Pregnancy Algorithm. Pharmacoepidemiology and Drug Safety. ISSN 1053-8569. 35(8). doi: 10.1002/pds.70438. Full text in Research Archive
• MacSweeney, Niamh; Dumoulin, Taleah Nanon; Aksnes, Eira Ranheim; Barth, Claudia; Crestol, Arielle & Heller, Carina [Show all 12 contributors for this article] (2026). Adolescent Hormonal Contraceptive Use in the Context of Brain Development and Depression Risk: A Review and Considerations for Future Research. Biological Psychiatry: Global Open Science. 6(5), p. 100758–100758. doi: 10.1016/j.bpsgos.2026.100758. Full text in Research Archive
• Trinh, Nhung; Fukasawa, Toshiki; Yanai, Takanori; Okura, Takayuki; Takayama, Atsushi & Sakai, Takamasa [Show all 9 contributors for this article] (2026). Paediatric outpatient antibiotic utilization patterns and use of healthcare services before, during and after the COVID-19 pandemic: interrupted time series analysis using data from Norway and Japan. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 81(7). doi: 10.1093/jac/dkag217. Full text in Research Archive
• Dolk, Helen; Damase-Michel, Christine; Morris, Joan; Neville, Amanda; Garne, Ester & Jordan, Sue [Show all 28 contributors for this article] (2026). The EUROmediCAT Network and Databases: A Resource for Pharmacovigilance in Pregnancy. Pharmacoepidemiology and Drug Safety. ISSN 1053-8569. 35(5). doi: 10.1002/pds.70360. Full text in Research Archive
• Damkier, Per; Gelder, Marleen van; Huybrechts, Krista F.; Meng, Lin Chieh; Hernandez-Diaz, Sonia & Nielsen, Jan [Show all 8 contributors for this article] (2026). Paternal use of metformin and risk of major congenital malformations: A meta-analysis of 4 studies. British Journal of Clinical Pharmacology. ISSN 0306-5251. 92(6), p. 1940–1943. doi: 10.1002/bcp.70547. Full text in Research Archive
• Baklouti, Sarah; Rigourd, Virginie; Panchaud, Alice; Nordeng, Hedvig Marie Egeland; Allegaert, Karel & Annaert, Pieter [Show all 10 contributors for this article] (2026). Population pharmacokinetic modelling of amoxicillin in human breast milk—A contribution from the ConcePTION project. British Journal of Clinical Pharmacology. ISSN 0306-5251. doi: 10.1002/bcp.70434. Full text in Research Archive
• Christensen, Jakob; Trabjerg, Betina B.; Gelder, Marleen van; Meng, Lin Chieh; Lai, Hsi Yu & Igland, Jannicke [Show all 12 contributors for this article] (2026). Risk of neurodevelopmental disorders associated with paternal use of valproate during spermatogenesis: a living meta-analysis—version 1. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. doi: 10.1136/jnnp-2026-338454. Full text in Research Archive
• Kinge-Rasmussen, Mathilde; Olstad, Emilie Willoch; Bjørk, Marte-Helene; Nordeng, Hedvig Marie Egeland; Tan, Manuela & Gervin, Kristina [Show all 7 contributors for this article] (2026). Genetic susceptibility for neurodevelopmental disorders in children born to women with epilepsy. Brain Communications. 8(2). doi: 10.1093/braincomms/fcag078. Full text in Research Archive Show summary

  Children of women with epilepsy have higher rates of neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), than the general population. This likely reflects a complex gene-environment interplay, but the specific contribution of genetic susceptibility, independent of in utero antiseizure medication exposure, remains unclear. The objective of this study was to evaluate whether polygenic risk scores (PRSs) for ADHD and ASD are elevated in these children compared to the general population and to assess associations with childhood neurodevelopmental traits. We analysed genetic and questionnaire data from the Norwegian Mother, Father and Child Cohort Study (MoBa). We included children born to women with epilepsy (n = 422) and children of mothers without epilepsy (n = 73 300). The parent-reported neurodevelopmental traits hyperactivity, inattention, social difficulties, language difficulties, repetitive behaviour and motor difficulties were measured using z scores at ages 0.5, 1.5, 3, 5 and 8 years. The genetic susceptibility was calculated as PRSs for ADHD and ASD. Children born to women with epilepsy had higher PRSs for ADHD (mean difference = 0.09, P = 0.07), not ASD (mean difference = 0.014, P = 0.78), compared to those without epilepsy. In these children, we observed stronger associations between the ADHD PRSs and neurodevelopmental traits closely linked to ADHD, specifically hyperactivity and inattention for all ages examined with the strongest association at 8 years. For the ASD PRSs, we observed stronger associations with motor development and language difficulties particularly at 5 years in children born to women with epilepsy. Although these associations were in the same direction and statistically significant for all ages in the general population, they did not reach statistical significance in children born to women with epilepsy. Findings from this study show that the ADHD and ASD PRSs were more strongly associated with hyperactivity/inattention, and with language/motor difficulties respectively in children born to women with epilepsy, compared to the general population. However, statistical significance was not reached likely due to limited sample size. These findings underscore the importance of considering genetic predisposition when assessing neurodevelopmental risks in this population.

• Zugic, Milica; Pejic, Natasa; Hayati, Saeed; Gelder, Marleen van & Nordeng, Hedvig Marie Egeland (2026). Development of a novel adherence scale for antidepressants in pregnancy: Results from a cross-sectional study. Exploratory Research in Clinical and Social Pharmacy (ERCSP). 21. doi: 10.1016/j.rcsop.2026.100704. Full text in Research Archive
• López-Güell, Kim; Català, Martí; Dedman, Daniel; Duarte-Salles, Talita; Kolde, Raivo & López-Blasco, Raúl [Show all 38 contributors for this article] (2025). Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries. Journal of Clinical Epidemiology. ISSN 0895-4356. 185. doi: 10.1016/j.jclinepi.2025.111867. Full text in Research Archive
• Mølgaard-Nielsen, Ditte; Mitter, Vera; Lupattelli, Angela; Hoxhaj, Vjola; Navarro, Constanza L. Andaur & Hayati, Saeed [Show all 23 contributors for this article] (2025). Identification of gestational diabetes mellitus in European electronic healthcare databases: insights from the ConcePTION project. BMJ Open. 15(10). doi: 10.1136/bmjopen-2025-102343. Full text in Research Archive
• Vallejo-Yagüe, Enriqueta; Vries, Sieta T. de; Parra-Casado, Daniel La; Gardarsdottir, Helga; Faquetti, Maria Luisa & Valkengoed, Irene van [Show all 27 contributors for this article] (2025). Advancing Health Equity in Europe: Explore, Tailor, Implement, and Evaluate (ETIE)—A Framework of Diversity and Fairness in Pharmacoepidemiologic Research. Pharmacoepidemiology and Drug Safety. ISSN 1053-8569. 34(7). doi: 10.1002/pds.70175. Full text in Research Archive
• Beslay, Marie; Geissbühler, Yvonne; Beau, Anna Belle; Messina, Davide; Benevent, Justine & Ballardini, Elisa [Show all 25 contributors for this article] (2025). Identifying multiple sclerosis in women of childbearing age in six European countries: a contribution from the ConcePTION project. European Journal of Epidemiology (EJE). ISSN 0393-2990. 40(8), p. 891–904. doi: 10.1007/s10654-025-01264-3. Full text in Research Archive Show summary

  Prevalence of Multiple Sclerosis (MS) has increased over the last decades, primarily among women of childbearing age. Several algorithms for identifying MS have been described in the literature, providing heterogeneous prevalence estimates. We compared five algorithms to identify MS in women of childbearing age and estimated MS prevalence by time period and age-group. The study population included women aged 15 to 49 years-old between 2005 and 2019, from three data sources including all women (from Italy, Norway, and Wales), and three including pregnant women only (from France, Finland, and Spain; data collected around pregnancy). Five algorithms were tested: MS1 to MS3 combined MS diagnoses and MS-medicine prescriptions/dispensations, requiring 1, 2, or 3 occurrences, respectively; MS4 and MS5 used only MS diagnoses, requiring at least 2 occurrences (MS4 allowed just 1 if diagnosis was from inpatient care). In 2015–2019, MS prevalence based on MS1 ranged from 109 to 359 per 100,000 women: 109 in France, 121 in Spain, 195 in Wales, 232 in Finland, 264 in Italy, and 359 in Norway. More restrictive algorithms led to greater disparity, with MS3 ranging from 53 in Spain to 325 in Norway, and MS5 from 21 in France to 345 in Norway. All algorithms showed expected prevalence trends by time and age among women of childbearing age, though lower than in the literature. Overall, MS1 provided prevalence estimates most closely aligned with existing literature. This study offers key insights into choosing algorithms for identifying MS in women of childbearing age and in pregnant women.

• Beau, Anna Belle; Paoletti, Olga; Bénévent, Justine; Beslay, Marie; Moisset, Xavier & Ballardini, Elisa [Show all 24 contributors for this article] (2025). Identifying Maternal Conditions Leading to Gabapentinoid Prescriptions in Pregnancy Using Electronic Health Records from Six European Countries: A Contribution from the IMI ConcePTION Project. Drug Safety. ISSN 0114-5916. 48(11), p. 1189–1204. doi: 10.1007/s40264-025-01565-2. Full text in Research Archive Show summary

  Introduction and Objective Given the recent increase in the prescription and dispensation of gabapentinoids (gabapentin and pregabalin) and the importance of controlling for underlying maternal illnesses in drug safety studies, we aimed to develop algorithms for identifying maternal conditions leading to gabapentinoid prescribing among pregnant women using data from six electronic healthcare data sources across Europe. Methods The study was conducted in Finland, France (Haute-Garonne), Italy (Emilia Romagna), Norway, Spain (Valencian region), and Wales (UK), covering three million pregnancies from 2006 to 2020. Algorithms were developed to detect epilepsy, neuropathic pain, and generalized anxiety disorder (GAD) (approved indications for gabapentinoids by the European Medicines Agency, with the exception of gabapentin for GAD) using data ± 1 year around the gabapentinoid prescription date. Data included prescriber specialty, primary and specialized health care diagnoses, and co-prescription/dispensation data. Additional analyses investigated potential unlicensed indications (such as fibromyalgia, restless legs syndrome, bipolar disorder) and potential for abuse (using codes for substance use disorders and alcohol withdrawal). Results Gabapentinoids were prescribed/dispensed in 1770 pregnancies (7.7 per 1000) in Spain, 2912 pregnancies (6.6 per 1000) in Wales, 3163 pregnancies (3.6 per 1000) in Norway, 2406 pregnancies (3.0 per 1000) in Finland, 908 pregnancies (2.2 per 1000) in Italy, and 269 pregnancies (1.9 per 1000) in France. A maternal condition related to gabapentinoid prescriptions was identified by the algorithm in 2797 (88.4%) in Norway, 2180 (74.9%) in Wales, 1269 (71.7%) in Spain, 1534 (63.8%) in Finland, 163 (60.6%) in France, and 396 (43.6%) pregnancies in Italy. Anxiety (licensed or unlicensed) was the most commonly captured condition in Wales (70.5%), Spain (51.5%), Finland (42.0%), and Italy (26.2%), whereas neuropathic pain prevailed in Norway (76.9%) and France (49.8%). Epilepsy was the least frequent maternal condition leading to gabapentinoid prescriptions across all data sources (below 15% of all pregnancies). The relative preponderance of these conditions differed between pregabalin and gabapentin. Additionally, unlicensed indications were captured in 0% to 13% of pregnancies, depending on the data source. The analyses of potential for abuse showed that records of alcohol withdrawal and/or substance use disorders (within 1 year before and after the gabapentinoids prescription/dispensation date) were present in 3% of pregnancies in Italy and up to 23% in Wales. Conclusions Our study provides valuable insights into gabapentinoid use during pregnancy, with anxiety being the most common condition among pregnant women with gabapentinoid prescriptions in Finland, Italy, Spain, and Wales, whereas neuropathic pain predominated in France and Norway. Moreover, we found that between 3 and 23% of these pregnancies were associated with substance abuse, underscoring the need for careful prescribing of commonly abused medicines. The proposed methods for detecting maternal conditions leading to prescribing will facilitate accurate assessment of medication use and safety during pregnancy, whilst addressing confounding by indication.

• Given, Joanne; Paoletti, Olga; Bromley, Rebecca; Ballardini, Elisa; Beau, Anna Belle & Bartolini, Claudia [Show all 20 contributors for this article] (2025). The Effect of Different Algorithms on Prevalence of Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder in Secondary Healthcare Data in Five European Countries: A Contribution from the ConcePTION Project. Journal of Autism and Developmental Disorders. ISSN 0162-3257. doi: 10.1007/s10803-025-06997-4. Full text in Research Archive Show summary

  To assess the effect on prevalence estimates of using different algorithms to identify children with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in healthcare data. Three algorithms were developed and run on administrative/research data in Finland, France (Haute Garonne), Italy (Emilia Romagna), Norway and Wales: (1) ≥ 1 ADHD or ASD diagnoses recorded in specialist settings, (2) ≥ 2 ADHD or ASD diagnoses recorded in primary care and (3) ≥ 1 prescription for medication to manage ADHD. Prevalence rates per 1000 children for each algorithm were calculated. 3,130,162 children (born 1996–2020) with 29,291,204 years of follow-up were included. ADHD prevalence per 1000 children in specialist settings ranged from 3.9 (Emilia Romagna) to 24.1 (Finland); and was 7.0 in primary care (Finland). Based on prescriptions, ADHD prevalence ranged from 0.1 (Emilia Romagna) to 9.9 (Haute Garonne). ASD prevalence in specialist settings ranged from 5.6 (Wales) to 9.7 (Finland), and in primary care from 1.0 (Finland) to 2.0 (Wales). Prevalence of ADHD and ASD was greater among children with longer follow-up. In Finland and Wales, 1.7% and 19.4% of children were diagnosed with ASD in primary care only respectively. The male:female ratio was 3–4:1. Whilst there was considerable geographical variation in the length of follow-up available, and prevalence of ADHD and ASD, specialist diagnoses recorded in healthcare data were key to identifying children with these disorders. These data sources can be complemented by using primary care diagnoses and prescription data to identify affected children more comprehensively.

• Zidan, Mahmoud; Trinh, Nhung; Desalegn, Anteneh Assefa; Smith, Louisa H.; Gelder, Marleen van & Nordeng, Hedvig Marie Egeland [Show all 7 contributors for this article] (2025). BNT162b2 mRNA COVID-19 vaccine effectiveness in pregnancy: Emulating trial NCT04754594 using observational data from Norwegian health registries. Vaccine. ISSN 0264-410X. 68. doi: 10.1016/j.vaccine.2025.127908. Full text in Research Archive
• Beslay, Marie; Beau, Anna Belle; Messina, Davide; Benevent, Justine; Ballardini, Elisa & Barrachina-Bonet, Laia [Show all 25 contributors for this article] (2025). Methods of estimating prevalence of multiple sclerosis in six European healthcare data sources: a contribution from the ConcePTION project. European Journal of Epidemiology (EJE). ISSN 0393-2990. doi: 10.1007/s10654-025-01243-8. Full text in Research Archive Show summary

  Multiple sclerosis (MS) is a chronic autoimmune condition primarily affecting women and often diagnosed during childbearing years. This study assessed the impact of the lookback period and calculation method on MS prevalence in three healthcare data sources including women of childbearing age (from Italy, Norway and Wales) and three data sources including pregnant women (from France, Finland and Spain). Women aged 15 to 49 years from 2005 to 2019 were included, data from pregnant women were collected around the pregnancy period. MS cases were identified based on at least one MS diagnosis or one dispensation for an MS-specific medication. All data sources provided inpatient diagnoses and medication data; outpatient diagnoses were available in Norway and Finland, and primary care diagnoses in Norway, Finland and Wales. We assessed MS case detection rate by lookback period, and compared three methods for estimating yearly MS prevalence: period prevalence (PP), average point prevalence (APP) and person-time prevalence (PTP). The estimated lookback periods to identify 95% of MS cases ranged from 6 to 9 years. APP and PTP provided lower prevalence estimates than PP, especially when the lookback to identify MS was short. In women of childbearing age, MS prevalence increased over time with all calculation methods and the highest MS prevalence was observed in Norway (PP of 402 per 100,000 in 2019). Finland showed the highest MS prevalence in pregnant women (PP of 218 per 100,000 in 2018). This study highlights the importance of sufficient lookback and available data to accurately estimate MS prevalence.

• Liu, Xiaoqin; Madsen, Kathrine Bang; Zhu, Jin Liang; Munk-Olsen, Trine; Damkier, Per & Lupattelli, Angela [Show all 13 contributors for this article] (2025). Psychotropic Medication Exposure via Breast Milk: A Population-Based Descriptive Study in Denmark. Paediatric and Perinatal Epidemiology. ISSN 0269-5022. 39(7), p. 612–625. doi: 10.1111/ppe.70074. Full text in Research Archive
• Macente, Julia; Nauwelaerts, Nina; Badée, Justine Marine; Bonan, Rodolfo Hernandes; Huang, Miao Chan & Neste, Martje Van [Show all 12 contributors for this article] (2025). Predicting Drug Transfer Into Human Milk With the Simcyp Simulator: A Contribution From the ConcePTION Project. CPT: Pharmacometrics and Systems Pharmacology (PSP). 14(9), p. 1470–1484. doi: 10.1002/psp4.70066. Full text in Research Archive
• Olstad, Emilie Willoch; Nordeng, Hedvig Marie Egeland; Bjørk, Marte-Helene; Selmer, Kaja Kristine & Gervin, Kristina (2025). Paternal valproate use and impact of shared genetic susceptibility on child neurodevelopment. Scientific Reports. 15(1). doi: 10.1038/s41598-025-23377-1. Full text in Research Archive
• Sakai, Takamasa; Nordeng, Hedvig Marie Egeland & Gelder, Marleen van (2025). Longitudinal Methods Versus Multiple Imputation to Infer Missing Maternal Data in Registry-Based Pregnancy Studies. Paediatric and Perinatal Epidemiology. ISSN 0269-5022. doi: 10.1111/ppe.70011. Full text in Research Archive Show summary

  Background: In birth registries, incomplete recording of information leads to missing values. Multiple imputation (MI) by chained equations is a widely used method for analysing datasets with missing data. It is unknown whether using registry records from multiple pregnancies contributed by the same woman could potentially give more accurate values when resolving missing data. Objectives: To investigate the relative performance of five methods to infer missing data on maternal characteristics using data from a medical birth registry, comparing longitudinal methods and MI with data from previous and future pregnancies. Methods: We used data from the Medical Birth Registry of Norway (MBRN), selecting records among mothers with more than one pregnancy between 2004 and 2018. Longitudinal methods used reference pregnancies in three time directions: past, future and closest pregnancy record. MI was conducted with only index pregnancy records (single-pregnancy MI) and with both index and closest reference pregnancy records (multiple-pregnancy MI). Validity was assessed by comparing the actual values with inferred/imputed values. For continuous variables, we calculated the proportion of inferred values within predefined increments. For binary variables, we calculated five parameters: agreement rate, sensitivity, specificity, positive predictive value and negative predictive value. Results: We included 578,670 pregnancies among 256,658 women. For continuous variables, the longitudinal methods showed the highest proportion within predefined increments, followed by multiple-pregnancy MI, and single-pregnancy MI showed the lowest value. For binary variables, longitudinal methods generally showed higher values among the five validity parameters than MI. Single-pregnancy MI had substantially lower agreement, while multiple-pregnancy MI performed similarly to longitudinal methods. Conclusions: The longitudinal method outperformed MI in inferring missing data on maternal characteristics in a medical birth registry.

• Carson, Alexis Christine; Trinh, Nhung; Nordeng, Hedvig Marie Egeland; Liu, Xiaoqin; Munk-Olsen, Trine & Eberhard-Gran, Malin [Show all 8 contributors for this article] (2025). Initiating antidepressant treatment in pregnancy: Timing, intensity, and influential maternal and familial factors. Journal of Affective Disorders. ISSN 0165-0327. 388. doi: 10.1016/j.jad.2025.119726. Full text in Research Archive Show summary

  Objective: To describe the timing and intensity of antidepressant initiation in pregnancy using longitudinal trajectories of antidepressant prescription fills to identify associated sociodemographic, lifestyle, somatic, mental health, pregnancy, and paternal factors. Methods: This population-based cohort within the Norwegian Mother, Father and Child Cohort study linked to MoBa Genetics and the Prescribed Drug Registry included 1879 women with a new episode of self-reported depression/anxiety during pregnancy. Antidepressants were measured by week and average daily dose. Results: There were 87 initiators, from which we identified three prescription fill trajectories: Early-pregnancy initiators with rapid discontinuation (n = 41, 47.1 %), Early-pregnancy initiators with mid-pregnancy discontinuation (n = 30, 34.5 %), and Early-mid pregnancy initiators with continuation (n = 16, 18.4 %) and three dose trajectories: Low dose with discontinuation (n = 45, 51.7 %), High dose with discontinuation (n = 26, 29.9 %), and Medium dose with continuation (n = 16, 18.4 %). Thyroid disorder was associated with Early initiators with rapid discontinuation (adjusted relative risk ratios (aRRR): 4.15, 95 % CI: 1.56–11.03) compared to Unmedicated. Other psychotropics pre-pregnancy increased the likelihood of being Early initiators with mid-pregnancy discontinuation and High dose discontinuers compared to Unmedicated. Higher maternal genetic liability for depression was strongly associated with Early initiators with mid-pregnancy discontinuation (aRRR = 8.57, 95 % CI: 3.09–23.74), High dose discontinuers and Medium dose continuers across comparisons. Adverse reproductive history, immigration and alcohol pre-pregnancy emerged as important factors. Conclusions: Approximately 5 out of 100 women with a new episode of depression/anxiety initiated an antidepressant during pregnancy, predominantly in early pregnancy, with most discontinuing early to mid-pregnancy. Identified factors can be utilized by clinicians to provide personalized treatment guidance.

• Hemmingsen, Caroline H.; Kjaer, Susanne K.; Andersen, Sarah Hjorth; Nörby, Ulrika; Pottegård, Anton & Mathiasen, René [Show all 11 contributors for this article] (2025). Maternal hormonal contraceptive use and childhood central nervous system tumor risk in a large Scandinavian cohort. International Journal of Cancer. ISSN 0020-7136. 157(8), p. 1557–1565. doi: 10.1002/ijc.35509. Full text in Research Archive Show summary

  An association between maternal hormonal contraception use and childhood central nervous system (CNS) tumors has been suggested, but findings are inconclusive. This population-based cohort study includes Scandinavian nationwide registry data on liveborn children (1996–2018). Children were followed from birth until CNS tumor (<20 years) or censoring (other cancer, emigration, death, 20th birthday, or end of follow-up in 2017–2020). Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between maternal hormonal contraception use (any type, type-specific) and CNS tumor risk (any, any malignant, type-specific). Maternal use was categorized as “recent use” (0–3 months before or during pregnancy, except for non-oral progestin-only types), “previous use” (before recent use), and “no use”. A total of 3,183,316 children were followed for 29,455,528 person-years, during which time 1384 children developed a CNS tumor (610 malignant). Compared with no use, maternal previous or recent use of any hormonal contraception (HR 0.93, 95% CI 0.82–1.05; HR 0.99, 95% CI 0.83–1.19), combined and progestin-only types (oral, non-oral), were not associated with childhood CNS tumor risk. However, maternal recent progestin-only injection use was associated with malignant childhood CNS tumors (HR 3.95, 95CI % 1.46–10.68), compared with no use (number needed to harm: 1 per 14,577 person-years). In conclusion, no association was found between maternal use of common types of hormonal contraception and CNS tumors in children. The rarely used progestin-only injections (medroxyprogesterone acetate) were associated with malignant CNS tumor risk in children, though based on few children.

• Bernhardsen, Guro Pauck; Pesonen, Maiju; Keski-Nisula, Leea; Nordeng, Hedvig Marie Egeland & Lehto, Soili Marianne (2025). Trajectories of Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Perinatal Outcomes: A Longitudinal Register Study. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. 133(1), p. 83–94. doi: 10.1111/1471-0528.18337. Full text in Research Archive
• Reddy, Akhila Srinivas; Gelder, Marleen van; Olstad, Emilie Willoch; Gervin, Kristina; Torkildsen, Janne von Koss & Nordeng, Hedvig Marie Egeland (2025). Prevalence of Neurodevelopmental Disorders in Families of Women Taking Psychotropic Medication During Pregnancy. Paediatric and Perinatal Epidemiology. ISSN 0269-5022. 40(1), p. 97–108. doi: 10.1111/ppe.70075. Full text in Research Archive Show summary

  Background Familial and environmental factors contribute to neurodevelopmental disorders (NDDs). Prenatal psychotropic exposure may influence the risk of NDDs in children. As these medications are prescribed to women with mental disorders, which are genetically and environmentally linked to NDDs, accounting for familial confounding is essential when studying medication safety in pregnancy. Objectives To compare the prevalence of NDDs in pregnant women using psychotropics, their partners, and their previous children, with those not using these medications. Methods We included data from the most recent pregnancy of Norwegian women with mental disorders who gave birth between 2010 and 2018, using Norwegian registries. Maternal psychotropic use included antidepressants, antipsychotics, anxiolytics, hypnotics, and sedatives, as recorded in the Norwegian Prescription Database. NDDs were identified using ICD-10 codes for intellectual disabilities, language/scholastic disorders, pervasive developmental disorders, and attention-deficit hyperactivity disorders (ADHD) from the Norwegian Patient Registry. Modified Poisson regression estimated crude and adjusted relative risks (aRRs) for the association between psychotropic use and family history of NDDs. Results The study included 27,638 women. Among psychotropic users, NDDs prevalence was 9.6% in women, 5.4% in partners, and 10.0% in previous children, compared to 5.7%, 4.6%, and 8.0% in non-users, respectively. ADHD was the most prevalent NDD. Psychotropic use in pregnancy was associated with any NDD, particularly ADHD, in the women [any NDD aRR 1.77 (95% CI 1.60, 1.95); ADHD aRR 1.79 (95% CI 1.61, 1.98)], previous children [any NDD aRR 1.25 (95% CI 1.07, 1.47); ADHD aRR 1.26 (95% CI 1.02, 1.54)], and partners [any NDD aRR 1.21 (95% CI 1.06, 1.37); ADHD aRR 1.22 (95% CI 1.07, 1.39)]. Conclusions Prenatal psychotropic use was associated with a higher prevalence of NDDs in mothers and their previous children, highlighting the need to account for familial neurodevelopmental patterns to distinguish the effects of psychotropics from underlying genetic or familial factors.

• Bruin, Odette de; Maisonneuve, Emeline; Hurley, Eimir; Nordeng, Hedvig Marie Egeland; Bérard, Anick & Sheehy, Odile [Show all 73 contributors for this article] (2025). Adverse outcomes among pregnant women with COVID‐19 according to hospitalization status: A prospective individual participant data meta‐analysis in Europe and North America. International Journal of Gynecology & Obstetrics. ISSN 0020-7292. p. 1–10. doi: 10.1002/ijgo.70694. Full text in Research Archive Show summary

  Abstract Background Understanding the varied impact of COVID‐19 severity on pregnancy outcomes is crucial for informed clinical management and targeted interventions. Objective To evaluate the impact of COVID‐19 on pregnancy outcomes, distinguishing between pregnant women managed in primary care and those requiring hospitalization. Search Strategy Regulatory authorities actively promoted global cooperation on COVID‐19's impact during pregnancy. Data were obtained through these regulatory bodies and direct researcher communication rather than through systematic searches. Selection Criteria Data sources required secondary population‐based data to identify pregnancies with COVID‐19, along with hospitalization, diagnostic and medication codes. Eligibility for the meta‐analysis was determined through protocol evaluation and researcher consultations. Data Collection and Analysis PRISMA‐IPD and Cochrane guidelines for prospective meta‐analysis were followed. Protocols and definitions were standardized across sources, and a common R script was developed. Initially, crude and adjusted relative risks (aRR) with 95% confidence intervals (CI) were calculated to assess adverse outcomes in pregnant women with and without COVID‐19 in each data source. Estimates were stratified by trimester at infection and hospitalization status. Subsequently, data were pooled using a random‐effects meta‐analysis. Main Results Data from 10 sources across seven countries contributed to the meta‐analysis, including 86 210 pregnant women diagnosed with COVID‐19, of whom 4.4% were hospitalized. Non‐hospitalized pregnant women with COVID‐19 had no increased risks of adverse outcomes compared to pregnant women without COVID‐19. However, hospitalized women with COVID‐19 in each trimester had higher risks of cesarean section, preterm birth, and LBW compared to pregnant women without COVID‐19. Hospitalization due to COVID‐19 in the third trimester was associated with increased risk of stillbirth (aRR 5.90, 95% CI: 2.22–15.71, I 2  = 0%). First‐trimester hospitalizations due to COVID‐19 did not show heightened risks of GDM (aRR 2.08, 95% CI: 0.93–4.64, I 2  = 65%), pre‐eclampsia (aRR 1.79, 95% CI: 0.48–6.66, I 2  = 71%), or major congenital anomalies (aRR 1.30, 95% CI: 0.55–3.06, I 2  = 0%). Conclusions and Relevance COVID‐19 requiring hospitalization is associated with adverse pregnancy outcomes, emphasizing the need to prevent severe illness during pregnancy. This study also highlights the importance of international collaboration for gathering pregnancy data and shows that building global research networks is essential for responding to future health crises.

• Bruin, Odette de; Maisonneuve, Emeline; Hurley, Eimir; Nordeng, Hedvig Marie Egeland; Bérard, Anick & Sheehy, Odile [Show all 75 contributors for this article] (2025). Medications Used Among Nonhospitalized Pregnant Women With COVID‐19: A Prospective Individual Patient Data Meta‐Analysis in Europe and North America. Pharmacoepidemiology and Drug Safety. ISSN 1053-8569. 35(1). doi: 10.1002/pds.70303. Full text in Research Archive Show summary

  ABSTRACT Aim To estimate the prevalence of medication use in nonhospitalized pregnant women with COVID‐19. Methods A prospective two‐stage individual patient meta‐analysis across 10 data sources in Europe and North America studied medication use among nonhospitalized pregnant women with COVID‐19 between January 2020 and December 2022. Comparisons were made between medication use within 30 days pre‐ and post‐COVID‐19 diagnosis in this cohort and two comparator groups: pregnant women without COVID‐19 and nonpregnant women with COVID‐19. Prevalence estimates were pooled using a random‐effects model stratified by trimester. Results 50 335 nonhospitalized pregnant women with COVID‐19 were identified. The pooled prevalence of antibacterial use in the third trimester was higher post‐COVID‐19 diagnosis (6.8%, 95% confidence interval [CI] = 5.5–8.4, I 2  = 94%) compared with the same women pre‐COVID‐19 (3.9%, 95% CI = 3.1–4.9, I 2  = 89%). Overall, pregnant women with COVID‐19 had higher medication use compared to pregnant women without COVID‐19, although the CIs of the prevalence overlapped. Post‐COVID‐19, antithrombotic prevalence was 4.5% (95% CI = 1.1–16.5, I 2  = 100%) among pregnant women with COVID‐19 in the third trimester, compared to 2.1% (95% CI = 1.2–3.6, I 2  = 99%) among those without COVID‐19 in the third trimester. Compared to nonpregnant women with COVID‐19, pregnant women with COVID‐19 were less likely to be prescribed analgesics, antiprotozoals, corticosteroids, psychoanaleptics and psycholeptics, and more likely to be prescribed antithrombotics, cough and cold and nasal preparations, and drugs used in diabetes across all trimesters. High heterogeneity existed in nearly all analyses. Conclusion This international meta‐analysis reveals low medication use and country‐specific variations, enhancing insight into the management of COVID‐19 in nonhospitalized pregnant women. Higher antithrombotic use post‐COVID‐19 suggests prophylactic treatment in this population, but variation between countries emphasizes the challenges of combining multinational data.

• Krogsrud, Stine Kleppe; Nordeng, Hedvig Marie Egeland; Roe, James Michael; Torkildsen, Janne von Koss; Wood, Mollie Elizabeth & Ystrøm, Eivind (2025). Associations between prenatal paracetamol exposure and brain development from ages 4–16: A longitudinal MRI study. Developmental Cognitive Neuroscience. ISSN 1878-9293. 78. doi: 10.1016/j.dcn.2025.101667. Full text in Research Archive Show summary

  Research has raised concerns regarding the potential impact of prenatal paracetamol exposure on fetal neurodevelopment. This is the first longitudinal study to investigate whether such exposure is related to structural brain development and cognitive abilities during childhood and adolescence. The sample includes 447 children aged 4.1–16.2 years with 905 MRI scans. The study is based on The Norwegian Mother, Father and Child Study (MoBa), and uses data from the Medical Birth Registry of Norway. The exposure variable is mothers’ self-reported use of paracetamol from prenatal and postnatal questionnaires. Among 447 children (229 girls; mean age 8.38 years), 193 (43.2 %) were prenatally exposed. Days of exposure range from 1 to 128 (mean 8.2). Vertex-wise linear mixed effect models showed that exposed children (n = 193; 393 scans) had slightly smaller cortical surface area and volume in some regions compared to non-exposed children. These results were seemingly driven by long-term exposed children (≥14 days in utero; n = 35; 72 scans, and exposed in all three trimesters, n = 21; 44 scans). However, group differences in brain structure were small with largely overlapping distributions, and the observational design and risk of unmeasured confounding preclude causal inference. Thus, the clinical significance remains uncertain. For cognitive abilities, results were reassuring showing no significant effect of prenatal paracetamol exposure on working memory capacity or IQ scores.

• Zugic, Milica; Trinh, Nhung; Rostami, Sina; Nordeng, Hedvig Marie Egeland; Ystrøm, Eivind & Bulik, Cynthia M [Show all 10 contributors for this article] (2025). Antenatal depressive and anxiety symptoms in women with eating disorders who continue or discontinue antidepressant treatment in pregnancy. Journal of Affective Disorders Reports. 22, p. 1–10. doi: 10.1016/j.jadr.2025.100985. Full text in Research Archive Show summary

  Background Limited evidence on antidepressant effectiveness in pregnant women with eating disorders (ED) challenges pharmacotherapy management. We examined antenatal depressive and anxiety symptoms with continued antidepressant use in women with ED. Methods We used data from the Norwegian Mother, Father and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway and MoBa Genetics. MoBa questionnaires at weeks 17 (early) and 30 (mid-late pregnancy) measured antidepressant exposure and symptoms of depression and anxiety using the 5-item Hopkins Symptom Checklist. We fitted generalised linear models and adjusted for confounding. In a subsample, we stratified analyses by polygenic-score tertiles for antidepressant response. Results We identified 5920 pregnancies in women with ED, mainly binge-eating disorder (BED) (84.0 %) and bulimia nervosa (BN) (12.4 %). Of these, 48 (0.8 %) continued antidepressants into early pregnancy, 93 (1.6 %) discontinued during, and 85 (1.4 %) discontinued before pregnancy. At early pregnancy only, continued antidepressant was associated with lower severity of depressive and anxiety symptoms relative to discontinuation. Among women with BED, this was specific to lower anxiety symptoms (β:-0.43, 95 %CI:-0.84, -0.02). This association was not observed in women with BN. In women with higher antidepressant-response polygenic-score continued antidepressant was associated with lower symptom severity relative to discontinued (range of β:-0.86 to -1.35). Conclusions Continuing antidepressants in early but not mid-late pregnancy is associated with lower severity of depressive and anxiety symptoms in women with BED. The association observed in women with higher antidepressant-response polygenic-score calls for larger studies on personalized treatment in perinatal ED.

• Christensen, Jacob J; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Lennep, Jeanine E Roeters van & Michelsen, Trond Melbye [Show all 8 contributors for this article] (2025). Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study. European Heart Journal. ISSN 0195-668X. 47(3), p. 318–327. doi: 10.1093/eurheartj/ehaf592. Full text in Research Archive Show summary

  Background and Aims Statins and other lipid-modifying agents (LMAs) have traditionally been contraindicated during pregnancy due to concerns about harmful fetal effects; however, the risks associated with exposure to statins and other LMAs in human pregnancies remain unclear. Therefore, this study aimed to examine the associations between statin and LMA exposure in pregnancy and congenital malformations in offspring, while updating a 2022 meta-analysis with the results from the present study. Methods National registry data were linked for all pregnant women in Norway in 2005–18. Associations between first-trimester statin prescription fills and congenital malformations were estimated with mixed-effects logistic regression, adjusting for age, parity, pre-pregnancy folate use, smoking in early pregnancy, comorbidity, and co-medication. Meta-analyses were performed with the generic inverse–variance method and random-effects model. Results Congenital malformations occurred among 34 755 out of 803 830 (4.3%) statin non-exposed pregnancies, 74 out of 1255 (5.9%) statin-discontinuer pregnancies, and 19 out of 283 (6.7%) statin-exposed pregnancies. Adjusted odds ratios (ORs) for exposed vs non-exposed pregnancies were 1.30 [95% confidence interval (CI) .81–2.09] for any, 1.15 (.61–2.19) for major, and 1.47 (.75–2.89) for minor malformations. In analyses of exposed vs discontinuer pregnancies, there were no associations between statin exposure and any (adjusted OR 1.01, 95% CI .59–1.72), major (1.08, .52–2.25), or minor malformations (.94, .44–2.00). Results were similar across sensitivity analyses. There was also no association between any LMA exposure and heart malformations (adjusted OR 1.22, 95% CI .50–3.01). The updated meta-analysis suggested no increased risk of major (adjusted OR 1.06, 95% CI .86–1.31) or heart malformations (1.24, 95% CI .94–1.64). Conclusions In this large, nationwide study and updated meta-analysis, no significant association was observed between first-trimester exposure to statins or other LMAs and congenital malformations. Although limited power may have prevented detection of weak but clinically relevant associations, the findings do not support a strong or independent association between statin exposure in pregnancy and congenital malformations.

• Neill, Thomas Boissiere-O; Gelder, Marleen van; Engjom, Hilde Marie & Nordeng, Hedvig Marie Egeland (2025). Exposure to Systemic Antimicrobials During Pregnancy and Risk of Miscarriage: A Population-Based Registry Study. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. doi: 10.1111/1471-0528.18155. Full text in Research Archive Show summary

  Objective To estimate miscarriage risk following gestational antimicrobial exposure while addressing biases that have affected previous studies. Design Population-based cohort study. Setting Linkage of four nationwide registries: Medical Birth Registry of Norway (MBRN), Norwegian Prescribed Drug Registry (NorPD), Norwegian Patient Registry (NPR) and Norwegian Control and Payment of Health Reimbursements Database (KUHR). Population or Sample A total of 704 082 pregnancies (2009–2018), with 91 836 (13.0%) exposed to systemic antimicrobials in early pregnancy. Methods Time-stratified Cox regression models with overlap weights were used, considering time-varying exposures and a 14-day lag to prevent reverse causation. Elective terminations were right-censored to address competing risks, with adjustment for common infections and probabilistic bias analysis for confounding by indication. Main Outcome Measures Miscarriage and gestational age at miscarriage, captured from NPR, KUHR and MBRN, using the UiO pregnancy algorithm. Results Nitrofurantoin, pivmecillinam and amoxicillin were not associated with increased miscarriage risk. Metronidazole (HR = 2.00; 95% CI: 1.82–2.21), ciprofloxacin (HR = 1.89; 95% CI: 1.62–2.20), cephalexin (HR = 1.87; 95% CI: 1.57–2.22), fluconazole (HR = 1.61; 95% CI: 1.45–1.78), trimethoprim-sulfas (HR = 1.49; 95% CI: 1.36–1.63) and others showed associations with miscarriage. Probabilistic bias analysis indicated that associations for common antimicrobials may be driven by the underlying infections. Conclusions Nitrofurantoin, pivmecillinam and amoxicillin did not increase miscarriage risk, but other less commonly used antimicrobials may carry higher risks. By addressing key biases, this study provided a more reliable assessment of miscarriage risks associated with antimicrobial use in early pregnancy.

• Sundbakk, Lene Maria; Wood, Mollie; Gran, Jon Michael & Nordeng, Hedvig Marie Egeland (2025). Prenatal exposure to benzodiazepine and z-hypnotics and fifth-grade scholastic skills—emulating target trials using data from the Norwegian Mother, Father and Child Cohort Study. American Journal of Epidemiology. ISSN 0002-9262. 194(1), p. 73–84. doi: 10.1093/aje/kwae159. Full text in Research Archive Show summary

  Evidence is limited regarding the effect of prenatal benzodiazepine and z-hypnotic exposure and long-term neurodevelopment in childhood. The objective of this study was to investigate the effects of initiating benzodiazepine or z-hypnotic treatment in early, mid, and late pregnancy on fifth-grade numeracy and literacy scholastic skills in children by emulating 3 target trials. The trials are identical except for the timing of enrollment and the number of eligible individuals. Eligibility to the trials required a history of anxiety and/or depression prior to pregnancy. We used data from the Norwegian Mother, Father and Child Cohort Study, linked to the Medical Birth Registry of Norway, to emulate the trials. We adjusted for baseline covariates that were available at time 0 for each trial by inverse probability of treatment weighting using the propensity score. The findings of this study did not show any effect of mothers’ initiation of treatment with benzodiazepines or z-hypnotics in early, mid, or late pregnancy on the children’s fifth-grade test scores in numeracy and literacy. The study results provide reassurance for patients in need of benzodiazepines and z-hypnotics during pregnancy; however, these findings need to be interpreted with caution due to low study power in some of the analyses.

• Hallberg, Adam; Aakjaer, Mia; Aaltonen, Katri; Andersen, Morten; Pedersen, Elisabeth & Hajiebrahimi, Mohammadhossein [Show all 10 contributors for this article] (2025). Epidemiological outcomes and policy implementation in the Nordic countries during the COVID-19 pandemic. Archives of Public Health. ISSN 0778-7367. 83(1). doi: 10.1186/s13690-025-01531-5. Full text in Research Archive Show summary

  Background During the initial phase of the COVID-19 pandemic, there was an intensive debate on which strategies would be most effective to minimize the negative societal impact of the pandemic. This study aimed to provide an overview of key epidemiological outcome measures of the disease in the Nordic countries and the subsequent policy implementation that were undertaken to curb the outbreak. Methods Time trends in test-positive infections, hospitalizations, and intensive care unit (ICU) admissions due to COVID-19 as well as COVID-19 mortality and excess mortality were compared between Denmark, Finland, Iceland, Norway, and Sweden. The epidemiological patterns were presented in relation to 13 different policies implemented to a different degree in the countries, eight of which were related to containment and five to health systems policy. A stringency index summarized the intensity of the policies. Data were collected from Our World in Data, the Oxford COVID-19 Government Response Tracker and Eurostat. The investigated time period was 1 January 2020 to 30 April 2022. Results Overall, Sweden had more infections, deaths, hospitalizations, and ICU admissions than the other Nordic countries during the first three waves of the pandemic. However, in the fourth wave, Denmark exceeded Sweden in all outcomes. The overall stringency among the Nordic countries varied broadly. The lowest average stringency index was observed in Iceland and the highest in Sweden. Excess mortality over the whole study period was lowest in Iceland while Norway had very few ICU admissions. Conclusions The Nordic countries took vastly different approaches to contain the spread of the pandemic, but the long-term impact on excess mortality was similar. The variety in policy responses and epidemiological measures bring many opportunities for learning across the countries.

• Reddy, Akhila Srinivas; Fawad, Fatima; Leite, Mila Apostolova; Olstad, Emilie Willoch; Gervin, Kristina & Kanduri, Chakravarthi [Show all 11 contributors for this article] (2025). Prenatal exposure to psychotropics and analgesics on cognitive, linguistic and educational outcomes – a scoping review with focus on validity and reliability of outcome measures. BMC Pregnancy and Childbirth. 25. doi: 10.1186/s12884-025-07235-6. Full text in Research Archive Show summary

  Objective To provide an overview of the observational studies on child’s cognitive, linguistic, and educational outcomes following prenatal exposure to psychotropics and analgesics, including reporting of outcome measure validity and reliability. Study design We searched four databases, MEDLINE, Embase, PsycINFO, and PubMed from inception to September 2023. We included all original studies involving participants less than 18 years old, who were prenatally exposed to psychotropics and/or analgesics with cognitive, linguistic, and/or educational outcomes and excluded those lacking comparison groups. Results 80 studies were identified. Most studies (47%) focused on the effects of prenatal exposure to antiepileptics on child cognition. Valproate was consistently associated with an increased risk of neurodevelopmental disorders, whereas the results for other medications were sparse and conflicting. Neurodevelopmental outcomes were measured by psychometric assessments in 71 studies and by diagnostic codes in health care registries in nine studies. Only 33 of the 71 studies (46.5%) using psychometric measures mentioned the psychometric properties of the instruments used. In studies using diagnostic outcome measures, only one study reported positive predictive values and performed a sensitivity analysis to address outcome misclassification. Conclusion Except for valproate, there is a concerning lack of studies on the impact of prenatal exposure to psychotropics and analgesics on cognitive, linguistic, and educational outcomes with existing studies yielding inconsistent findings. Regardless of whether psychometric measures or diagnostic codes were used, most studies lacked a robust assessment of outcome measures, which threatens their validity and interpretability. Future studies on long-term prenatal medication safety need to focus on the accuracy of neurodevelopmental outcome measures.

• Johnson, Hannah; Andersen, Sarah Hjorth; Morris, Joan; Pottegård, Anton; Leinonen, Maarit & Norby, Ulrika [Show all 7 contributors for this article] (2025). Use of signal detection methods to identify associations between prenatal medication exposure and subsequent childhood cancers: a Nordic hypothesis-generating registry-based study. Expert Opinion on Drug Safety. ISSN 1474-0338. p. 1–12. doi: 10.1080/14740338.2025.2461204. Full text in Research Archive
• Durán, Carlos E.; Riefolo, Fabio; Gini, Rosa; Barbieri, Elisa; Messina, Davide & Garcia, Patricia [Show all 16 contributors for this article] (2025). Incidence of severe and non-severe SARS-CoV-2 infections in children and adolescents: a population-based cohort study using six healthcare databases from Italy, Spain, and Norway. European Journal of Pediatrics. ISSN 0340-6199. 184. doi: 10.1007/s00431-024-05864-1. Full text in Research Archive
• Olstad, Emilie Willoch; Nordeng, Hedvig Marie Egeland; Bjørk, Marte-Helene; Selmer, Kaja Kristine & Gervin, Kristina (2025). Agreement Between Parental Self-Reported Antiseizure Medication Use and Dispensed Prescription Records From a National Prescription Database. Pharmacoepidemiology and Drug Safety. ISSN 1053-8569. 34(4). doi: 10.1002/pds.70139. Full text in Research Archive
• Abellan, Alicia; Burn, Edward; Trinh, Nhung; Burkard, Theresa; Callahan, Alison & Fernández-Bertolín, Sergio [Show all 12 contributors for this article] (2025). Expanding the OMOP Common Data Model to Support Perinatal Research in Network Studies. Pharmacoepidemiology and Drug Safety. ISSN 1053-8569. 34(2). doi: 10.1002/pds.70106. Full text in Research Archive
• Camanni, Margherita; Gelder, Marleen van; Cantarutti, Anna; Nordeng, Hedvig Marie Egeland & Lupattelli, Angela (2025). Association of Prenatal Exposure to Triptans, Alone or Combined With Other Migraine Medications, and Neurodevelopmental Outcomes in Offspring. Neurology. ISSN 0028-3878. 104(12). doi: 10.1212/WNL.0000000000213678. Full text in Research Archive Show summary

  Background and Objectives: The long-term reproductive safety of migraine medications remains uncertain. This study sought to examine the effect of different intensities and durations of prenatal exposure to triptans, alone and combined with other preventive migraine medications, on neurodevelopmental disorders (NDDs) in children. Methods: This nationwide health registry study in Norway included pregnancies of women with migraine before pregnancy and followed up their children up to 14 years of age. Single and multiple group-based trajectory models and group-based multitrajectory models were applied to cluster triptan exposure alone and combined with preventive antimigraine medications. Child outcomes, based on specialist outpatient and inpatient diagnoses, included autism spectrum and behavioral disorders, learning and intellectual disabilities, speech/language and developmental coordination disorders, and attention-deficit hyperactivity disorders (ADHDs). We fit adjusted and weighted pooled logistic regression models and standardized risk curves using propensity score–based overlap weighting. Results: We included 26,210 pregnancies of women with migraine; 4,929 and 21,281 were, respectively, nonmedicated and medicated with triptans in the year of prepregnancy. In the latter group, we identified 4 group-based trajectories of triptans alone and combined with preventive medications: discontinuers before (low use) (41.5%, 47.0%), early discontinuers (short-term low use) (31.3%, 28.8%), late discontinuers (moderate use) (21.3%, 9.1%), and late discontinuers (high use) (5.9%, 15.2%). Overall, 1,140 children (4.3%) had a NDD (mean follow-up time: 8 years). Children born to women with any triptan trajectory had a slightly higher risk of NDD compared with children of nonmedicated women (magnitude range of the weighted hazard ratio [wHR]: 1.05–1.16). These risks decreased to the null when discontinuers before (low use) acted as a comparator (magnitude of wHR: 0.94–1.01) or when analyzing speech/language disorders or ADHD (magnitude of wHR: 0.82–1.14). There was a slightly elevated risk of autism disorders with both triptan late discontinuation trajectories (wHR 1.24, 95% CI [0.78–1.97]; wHR 1.30, 95% CI [0.66–2.56]), but the 95% CI crossed the null and the weighted risk difference remained low. Discussion: Our findings indicate that prenatal exposure to triptans, alone or combined with other migraine medications, does not substantially increase the risk of a broad range of neurodevelopmental outcomes in children up to adolescence.

• Hemmingsen, Caroline H.; Kjaer, Susanne K.; Andersen, Sarah Hjorth; Nörby, Ulrika; Broe, Anne & Pottegård, Anton [Show all 13 contributors for this article] (2025). Maternal use of hormonal contraception and risk of childhood leukemia: A Scandinavian population-based cohort study. European Journal of Cancer. ISSN 0959-8049. 215. doi: 10.1016/j.ejca.2024.115168. Full text in Research Archive
• Xie, Junqing; López-Güell, Kim; Dedman, Daniel; Duarte-Salles, Talita; Kolde, Raivo & López-Blasco, Raúl [Show all 38 contributors for this article] (2024). Incidence of post-acute COVID-19 symptoms across healthcare settings in seven countries: an international retrospective cohort study using routinely-collected data. EClinicalMedicine. 77. doi: 10.1016/j.eclinm.2024.102903. Full text in Research Archive Show summary

  Background The World Health Organisation (WHO) has identified a range of symptomatic manifestations to aid in the clinical diagnosis of post-COVID conditions, herein referred to as post-acute COVID-19 symptoms. We conducted an international network cohort study to estimate the burden of these symptoms in North American, European, and Asian populations. Methods A federated analysis was conducted including 10 databases from the United Kingdom, Netherlands, Norway, Estonia, Spain, France, South Korea, and the United States, between September 1st 2020 and latest data availability (which varied from December 31st 2021 to February 28th 2023), covering primary and secondary care, nationwide registries, and claims data, all mapped to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We defined two cohorts for the main analyses: a SARS-CoV-2 infection cohort [positive polymerase chain reaction (PCR) or rapid lateral flow test (LFT) result or clinical COVID-19 diagnosis] and a general population cohort. Individuals with less than 365 days of prior history or 120 days of follow-up were excluded. We estimated incidence rates (IRs) of the 25 WHO-proposed post-acute COVID-19 symptoms, considering symptoms that occurred ≥90 and ≤365 days after index date, excluding individuals with the respective symptoms 180 days prior to the index event. Stratified analyses were conducted by age and sex. Incidence rate ratios (IRRs) were calculated comparing rates in the infected cohort versus the general population. Results from the different databases were combined using random-effects meta-analyses. Findings 3,019,408 individuals were included in the infection cohort. 1,585,160 of them were female and 1,434,248 of them male. 929,351,505 individuals were included in the general population group. 461,195,036 of them were female and 466,022,004 of them male. The 1-year IR of any post-acute COVID-19 symptom in the COVID-19 infection cohort varied significantly across databases, from 4.4 (95% CI 3.8–5.1) per 100 person-years to 103.9 (95% CI 103.2–104.7). The five most common symptoms were joint pain (from 1.6 (95% CI 1.3–1.9) to 14.3 (95% CI 14.1–14.6)), abdominal pain (from 0.3 (95% CI 0.1–0.5) to 9.9 (95% CI 9.7–10.1)), gastrointestinal issues (from 0.6 (95% CI 0.4–0.9) to 13.3 (95% CI 13.1–13.6)), cough (from 0.3 (95% CI 0.2–0.5) to 9.1 (95% CI 8.9–9.3)), and anxiety (from 0.8 (95% CI 0.6–1.2) to 11.4 (95% CI 11.2–11.6)); whereas muscle spasms (from 0.01 (95% CI 0.008–0.2) to 1.7 (95% CI 1.6–1.8)), pins and needles (from 0.05 (95% CI 0.03–0.0.9) to 1.5 (95% CI 1.4–1.6)), memory issues (from 0.03 (95% CI 0.02–0.06) to 0.8 (95% CI 0.7–0.8)), cognitive dysfunction (from 0.007 (95% CI 0.004–0.01) to 0.6 (95% CI 0.4–0.8)), and altered smell and/or taste (from 0.04 (95% CI 0.03–0.04) to 0.7 (95% CI 0.6–0.8)) were least common. Incidence rates of any post-acute COVID-19 symptoms generally increased with age, with certain symptoms peaking in middle-aged adults (anxiety, depressive disorders, headache, altered smell and taste) and others in pre-school children (gastrointestinal issues and cough). Females had higher incidence rates for most symptoms. Based on the random-effects model, the infected cohort had a higher incidence of any post-acute COVID-19 symptom than the general population, with a meta-analytic incidence rate ratio (meta-IRR) of 1.4 (1–2). A similar pattern was seen for all individual symptoms. The highest meta-IRRs were depressive disorder, 2.6 (1.7–3.9); anxiety, 2.3 (1.4–3.8); allergy, 2.1 (1.7–2.8) and sleep disorders, 2.1 (1.5–2.6). The meta-IRR for altered smell and/or taste was 1.9 (1.3–2.8). Interpretation Post-acute COVID-19 symptoms, as listed by the WHO, were commonly observed following COVID-19 infection. However, even after standardising research methods, there was significant heterogeneity in the incidence rates from different healthcare settings and geographical locations. This is the first international study of the epidemiology of post-acute COVID-19 symptoms using the WHO-listed symptoms. Its findings contibute to understand the epidemiology of this condition from a multinational approach. Limitations of this study include the lack of consensus of the post-acute COVID-19 definition, as well as the difficulty to capture the impact on daily life of the post-acute COVID-19 symptoms in the available datasets. Funding This work has been funded by the European Health Data Evidence Network (EHDEN) through an Evidence Generation Fund Grant and by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).

• Melander, Erik; Nielsen, Elisabet I.; Lindqvist, Annika; Hovd, Markus; Gandia, Peggy & Panchaud, Alice [Show all 11 contributors for this article] (2024). Population pharmacokinetic modelling of cetirizine concentrations in human breast milk—A contribution from the ConcePTION project. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 136(1). doi: 10.1111/bcpt.14100. Full text in Research Archive
• Mitter, Vera; Lupattelli, Angela; Bjørk, Marte-Helene & Nordeng, Hedvig Marie Egeland (2024). Identification and characterization of migraine in pregnancy: A Norwegian registry-based cohort study. Cephalalgia. ISSN 0333-1024. 44(4). doi: 10.1177/03331024241248846. Full text in Research Archive Show summary

  Background: Migraine is common in women of reproductive age. Migraine's episodic manifestation and acute and preventive pharmacological treatment options challenge studying drug safety for this condition during pregnancy. To improve such studies, we aimed to develop algorithms to identify and characterize migraines in electronic healthcare registries and to assess the level of care. Methods: We linked four registries to detect pregnancies from 2009-2018 and used three algorithms for migraine identification: i) diagnostic codes, ii) triptans dispensed, and iii) a combination of both. We assessed migraine severity using dispensed drugs as proxies. ICD-10 diagnostic subcodes of migraine (G43) allowed the allocation of four subtypes: complicated and/or status migrainosus; with aura; without aura; other/unspecified. Results: We included 535,089 pregnancies in 367,908 women with available one-year lookback. The prevalence of migraines identified was 2.9%-4.3% before, and 0.8%-1.5% during pregnancy, depending on algorithm used. Pregnant women with migraine were mostly managed in primary care. Conclusions: Primary care data in combination with drug dispensation records were instrumental for identification of migraine in electronic healthcare registries. Data from secondary care and drug dispensations allow better characterization of migraines. Jointly, these algorithms may contribute to improved perinatal pharmacoepidemiological studies in this population by addressing confounding by maternal migraine indication.

• Hurley, Eimir; Geisler, Benjamin Peter; Lupattelli, Angela; Poblador-Plou, Beatriz; Lassalle, Régis & Jové, Jérémy [Show all 30 contributors for this article] (2024). COVID-19 and pregnancy: A European study on pre- and post-infection medication use. European Journal of Clinical Pharmacology. ISSN 0031-6970. 80, p. 707–716. doi: 10.1007/s00228-024-03639-z. Full text in Research Archive Show summary

  Purpose The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. Methods We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. Results The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1–2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. Conclusion Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes.

• Elyass, Jovan; Desalegn, Anteneh Assefa; Trinh, Nhung; Orangzeb, Saima; Zidan, Mahmoud & Nordeng, Hedvig Marie Egeland [Show all 7 contributors for this article] (2024). Individual and familial factors associated with mRNA COVID-19 vaccine uptake in pregnancy: A large-scale registry-based linkage study. Vaccine. ISSN 0264-410X. 42(21). doi: 10.1016/j.vaccine.2024.126171. Full text in Research Archive Show summary

  The association between maternal COVID-19 vaccination in pregnancy and factors such as high risk for severe COVID-19, pre-existing asthma, prior adverse reproductive history, or paternal COVID-19 vaccination during pregnancy, remains unclear. The aim of this study is two-fold: (i) to describe uptake of COVID-19 vaccine during pregnancy by maternal risk for severe COVID-19 and asthma, and (ii) to comprehensively examine individual and familial factors associated with vaccine uptake during pregnancy in Norway. Based on nation-wide registry-linkage data in Norway, we included 101,659 deliveries with gestational length ≥12 weeks, in 2021–2022. Our outcome measure was uptake of at least one dose of mRNA COVID-19 vaccine during pregnancy, using a narrow (first ever dose) and broad (any dose) definition. We fit univariate and multivariate modified Poisson regression models, clustered by county of residency and adjusted for calendar time, to estimate risk ratios (RR) with 95 % Confidence Intervals (CIs). Gestational uptake of any COVID-19 vaccine dose increased from <1 % before mid Aug-2021, to 38.8 % in the rest of 2021, and 48.9 % in 2022. Only 28.8 % and 33.9 % pregnant individuals with high risk for severe COVID-19 or asthma, respectively, received at least one COVID-19 vaccine dose. Paternal COVID-19 vaccination was strongly associated with greater vaccine uptake by pregnant individuals (adjusted RR: 7.2, 95 % CI: 6.8–7.5). Maternal SARS-CoV-2 infection pre-pregnancy (adjusted RR: 0.31, 95 % CI: 0.26, 0.37), familial and individual migrant status were associated with a considerable decreased likelihood of vaccine uptake in pregnancy. History of miscarriage or pregnancy with congenital anomaly were not associated with vaccine uptake. Despite rising COVID-19 vaccine rates in pregnancy, uptake remained low for high-risk individuals. Paternal vaccination, pre-pregnancy infection, migration status, and maternal citizenship were strongly associated with prenatal vaccine uptake. This knowledge can inform tailoring of future vaccination campaigns.

• Orangzeb, Saima; Desalegn, Anteneh Assefa; Trinh, Nhung; Zhao, Jing; Nordeng, Hedvig Marie Egeland & Lupattelli, Angela (2024). COVID-19 vaccine uptake among children and adolescents in Norway: A comprehensive registry-based cohort study of over 800,000 individuals. Vaccine. ISSN 0264-410X. 42(15), p. 3420–3428. doi: 10.1016/j.vaccine.2024.04.039. Full text in Research Archive Show summary

  Factors related with COVID-19 vaccine uptake in children and adolescents in Norway remain unclear, despite this being useful knowledge for future pandemic preparedness. This study aimed to comprehensively examine individual and familial factors associated with vaccine uptake in children and adolescents in Norway. We utilized nationwide registry-data from various health registries and Statistics Norway, encompassing all children and adolescents living in Norway during the pandemic, until 31-Dec-2022. Vaccine uptake is defined as receiving at least one dose of COVID-19 vaccine. We employed a forward stepwise logistic regression model and a random forest machine-learning algorithm to explore the relationship between vaccine uptake and socio-cultural, demographic, and health-related factors. We included 423,548 5–11-year-olds, 269,830 12–15-year-olds, and 120,854 16–17-year-olds. Vaccine uptake in these three groups was respectively 2.6 %, 73.3 %, and 87.3 %. Factors associated with vaccine uptake varied by age group. In youngest children, immigrant background (Odds-ratio (OR) = 1.58, 95 % confidence interval (CI) (1.14–2.19)), born extremely preterm (OR = 2.38, 95 % CI (1.60–3.54)), having risk of severe COVID-19 (OR = 5.40, 95 % CI (4.69–6.23) and maternal COVID-19 vaccination (OR = 6.34, 95 % CI (5.35–7.53)) were positively associated with vaccine uptake. The latter two factors were also strongly, positively associated with vaccine uptake in 12–15-year-olds, while previous SARS-CoV-2 infection was negatively associated (OR = 0.12, 95 % CI (0.11–0.14). Similar findings were observed in 16–17-year-olds. COVID-19 vaccine uptake differed markedly by age group, and major associated factors included socio-demographics and parental COVID-19 vaccination status, prior SARS-CoV-2 infection, but also being born premature and having moderate or high risk of severe COVID-19.

• Monfort, Anaëlle; Cardoso, Evelina; Eap, Chin B.; Ansermot, Nicolas; Crettol, Severine & Fumeaux, Céline J. Fischer [Show all 21 contributors for this article] (2024). A population pharmacokinetic model for sertraline in women during the perinatal period—A contribution from the ConcePTION project. British Journal of Clinical Pharmacology. ISSN 0306-5251. 90(11), p. 2849–2860. doi: 10.1111/bcp.16177. Full text in Research Archive
• Rohweder, Ricardo; Pereira, Natálya G.; Micheletti, Bruna H.; Mosello, Jéssica; Campos, Júlia R. M. & Pereira, Matheus G. [Show all 15 contributors for this article] (2024). Medication Use Among Pregnant Women With SARS-CoV-2 Infection and Risk of Hospitalization—A Study in Two Brazilian Hospitals. Journal of Pregnancy. ISSN 2090-2727. 2024. doi: 10.1155/2024/8915166. Full text in Research Archive
• Meng, Lin-Chieh; Gelder, Marleen van; Chuang, Hui-Min; Chen, Liang-Kung; Hsiao, Fei-Yuan & Nordeng, Hedvig Marie Egeland (2024). Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study. The BMJ. 387. doi: 10.1136/bmj-2024-080127. Full text in Research Archive Show summary

  Objective To evaluate the association between paternal metformin use and risk of congenital malformations in offspring. Design Population based, cross national cohort study. Setting Norway and Taiwan. Participants 619 389 offspring with paternal data during the period of sperm development (three months before pregnancy) in the Norwegian cohort during 2010-21 and 2 563 812 in the Taiwanese cohort during 2004-18. Main outcome measures The primary outcome was any congenital malformation, and the secondary outcome was organ specific malformations, classified according to the European surveillance of congenital anomalies guidelines. Relative risks were estimated with an unadjusted analysis and with analyses restricted to the cohort of men with type 2 diabetes mellitus and those using overlap propensity score weighting to control for severity of diabetes and other potential confounders. Sibling matched comparisons were conducted to account for genetic and lifestyle factors. Relative risk estimates for Norwegian and Taiwanese data were pooled using a random effects meta-analytical approach. Results Paternal data on metformin use during the period of sperm development was available for 2075 (0.3%) offspring in Norway and 15 276 (0.6%) offspring in Taiwan. Among these offspring, 104 (5.0%) in Norway and 512 (3.4%) in Taiwan had congenital malformations. Increased risks of any congenital malformation associated with paternal metformin use were observed in the unadjusted analysis and attenuated with increasing control of confounding. The relative risks of any malformations with paternal metformin use were 1.29 (95% confidence interval 1.07 to 1.55) in Norway and 1.08 (0.99 to 1.17) in Taiwan in the unadjusted analysis and 1.20 (0.94 to 1.53) and 0.93 (0.80 to 1.07), respectively, in the analysis restricted to fathers with type 2 diabetes mellitus. In the overlap propensity score weighting analysis restricted to fathers with type 2 diabetes mellitus, the relative risks were 0.98 (0.72 to 1.33) in Norway and 0.87 (0.74 to 1.02) in Taiwan, resulting in a pooled estimate of 0.89 (0.77 to 1.03). No associations were observed between paternal metformin use and any organ specific malformations. These findings were consistent in sibling matched comparisons and sensitivity analyses. Conclusions The findings suggest that paternal use of metformin during the period of sperm development is not associated with congenital malformations in offspring, including organ specific malformations. Metformin can therefore continue to be considered a suitable initial oral agent for managing glucose levels in men with type 2 diabetes mellitus who plan on having children.

• Spildrejorde, Mari Roberts; Leithaug, Magnus; Samara, Athina; Aass, Hans Christian; Sharma, Ankush & Acharya, Ganesh [Show all 9 contributors for this article] (2024). Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression. Frontiers in Cell and Developmental Biology. 12. doi: 10.3389/fcell.2024.1428538. Full text in Research Archive Show summary

  Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed to investigate the impact of citalopram exposure on early neuronal differentiation of human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent effects on gene expression and DNA methylation of genes involved in neurodevelopmental processes or linked to depression, such as BDNF, GDF11, CCL2, STC1, DDIT4 and GAD2. Single-cell RNA-sequencing analysis revealed distinct clusters of stem cells, neuronal progenitors and neuroblasts, where exposure to citalopram subtly influenced progenitor subtypes. Pseudotemporal analysis showed enhanced neuronal differentiation. Our findings suggest that citalopram exposure during early neuronal differentiation influences gene expression patterns associated with neurodevelopment and depression, providing insights into its potential neurodevelopmental impact and highlighting the importance of further research to understand the long-term consequences of prenatal SSRI exposure.

• Mercadé-Besora, Núria; Li, Xintong; Kolde, Raivo; Trinh, Nhung; Sanchez-Santos, Maria T. & Man, Wai Yi [Show all 16 contributors for this article] (2024). The role of COVID-19 vaccines in preventing post-COVID-19 thromboembolic and cardiovascular complications. Heart. ISSN 1355-6037. 110(9). doi: 10.1136/heartjnl-2023-323483. Full text in Research Archive Show summary

  Objective To study the association between COVID-19 vaccination and the risk of post-COVID-19 cardiac and thromboembolic complications. Methods We conducted a staggered cohort study based on national vaccination campaigns using electronic health records from the UK, Spain and Estonia. Vaccine rollout was grouped into four stages with predefined enrolment periods. Each stage included all individuals eligible for vaccination, with no previous SARS-CoV-2 infection or COVID-19 vaccine at the start date. Vaccination status was used as a time-varying exposure. Outcomes included heart failure (HF), venous thromboembolism (VTE) and arterial thrombosis/thromboembolism (ATE) recorded in four time windows after SARS-CoV-2 infection: 0–30, 31–90, 91–180 and 181–365 days. Propensity score overlap weighting and empirical calibration were used to minimise observed and unobserved confounding, respectively. Fine-Gray models estimated subdistribution hazard ratios (sHR). Random effect meta-analyses were conducted across staggered cohorts and databases. Results The study included 10.17 million vaccinated and 10.39 million unvaccinated people. Vaccination was associated with reduced risks of acute (30-day) and post-acute COVID-19 VTE, ATE and HF: for example, meta-analytic sHR of 0.22 (95% CI 0.17 to 0.29), 0.53 (0.44 to 0.63) and 0.45 (0.38 to 0.53), respectively, for 0–30 days after SARS-CoV-2 infection, while in the 91–180 days sHR were 0.53 (0.40 to 0.70), 0.72 (0.58 to 0.88) and 0.61 (0.51 to 0.73), respectively. Conclusions COVID-19 vaccination reduced the risk of post-COVID-19 cardiac and thromboembolic outcomes. These effects were more pronounced for acute COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough versus unvaccinated SARS-CoV-2 infection.

• Ukah, Ugochinyere Vivian; Platt, Robert William & Nordeng, Hedvig Marie Egeland (2024). Impact of COVID-19 Pandemic on Dispensing of Cardiovascular Drugs in Norway: An Interrupted Time Series Study. American Journal of Preventive Medicine. ISSN 0749-3797. 66(4), p. 672–680. doi: 10.1016/j.amepre.2023.11.008. Full text in Research Archive Show summary

  Introduction The COVID-19 pandemic resulted in changes in prescription patterns and fillings for certain medications, but little is known about its impact on the dispensing of cardiovascular drugs. Methods Trends in dispensing of cardiovascular drugs before and during the pandemic were examined using a population-based cohort in Norway. Using interrupted time series analyses and considering March 1, 2020 as the interruption point, the impact of the pandemic on defined daily dose dispensing of prescribed cardiovascular drugs was estimated in a population of adults with and without pre-existing cardiovascular disease from January 2018 to December 2021. All data were analyzed in 2023. Results In a total of 4,053,957 adults, 690,910 (17.0%) had pre-existing cardiovascular disease. Prior to the pandemic, there was a significant monthly increase in any cardiovascular drug dispensing among those with pre-existing cardiovascular disease (0.30 defined daily dose per month per adult), including prescription of diuretics, calcium channel blockers, and lipid-modifying agents. After controlling for preinterruption trends, there was a slight decrease in level change immediately after the start of the pandemic (2.5 defined daily dose per month per adult) but an increase in the postinterruption trend (0.06 defined daily dose per month per adult) for dispensing of cardiovascular prescriptions, although these changes were not significant. Conclusions Although the COVID-19 pandemic did not appear to result in significant changes in patterns of cardiovascular drug dispensing in Norway, continued access to cardiovascular drugs remains important to prevent further related morbidity.

• Català, Martí; Mercadé-Besora, Núria; Kolde, Raivo; Trinh, Nhung; Roel, Elena & Burn, Edward [Show all 15 contributors for this article] (2024). The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia. The Lancet Respiratory Medicine. ISSN 2213-2600. 12(3), p. 225–236. doi: 10.1016/S2213-2600(23)00414-9. Full text in Research Archive Show summary

  Background Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2). Methods We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates. Findings A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44–0·67) in CPRD GOLD, 0·48 (0·34–0·68) in CPRD AURUM, 0·71 (0·55–0·91) in SIDIAP, and 0·59 (0·40–0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60–1·20] in CPRD GOLD and 0·84 [0·74–0·94] in CPRD AURUM). Interpretation Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults.

• Pedersen, Elisabeth; Tripodi, Elena; Aakjær, Mia; Li, Huiqi; Cantarutti, Anna & Nyberg, Fredrik [Show all 9 contributors for this article] (2024). Drug utilisation in children and adolescents before and after the start of the COVID-19 pandemic: Interrupted time-series analyses in three European countries. Paediatric and Perinatal Epidemiology. ISSN 0269-5022. 38(6), p. 450–460. doi: 10.1111/ppe.13046. Full text in Research Archive Show summary

  Background The COVID-19 pandemic has affected children and adolescents in several ways, including worsened mental health, improvement of asthma, and increases in diabetes ketoacidosis. Less is known about how medication use in children and adolescents has been affected by the pandemic. Objectives To explore how the COVID-19 pandemic affected drug utilisation in children and adolescents in Norway, Sweden, and Italy, by child age. Methods We conducted a longitudinal drug utilisation study among all children and adolescents (<18 years old) in Norway and Sweden and a nationwide paediatric database covering 3% of the paediatric population in Italy. We conducted an interrupted time-series analysis from January 2018 to December 2021, with March 2020 as the interruption point. Dispensing or prescription rates of antidepressants, anxiolytics, sleep medications, attention-deficit/hyperactivity disorder (ADHD) medications, insulin, and asthma medications were examined. Results The study population in January 2018 consisted of 3,455,521 children and adolescents (136,188 from Italy, 1,160,431 from Norway, and 2,158,902 from Sweden). For sleep medications and insulin, there were only minor changes in level or trend in some age groups after March 2020. For asthma medications, the pandemic was associated with an immediate decrease in dispensing in Norway and Sweden (range of change in level: −19.2 to −3.7 dispensings per 1000 person-months), and an increasing trend in all countries afterward (range of change in trend: 0.3–6.4 dispensings per 1000 person-months), especially for the youngest age groups. Among adolescents, the pandemic was associated with an increased trend for ADHD medications, antidepressants, and anxiolytics in Norway and Sweden, but not in Italy. Conclusions The increasing trend of psychotropic medication dispensing, especially among adolescents after the start of the pandemic, is concerning and should be investigated further. Aside from a temporary effect on asthma medication dispensing, the pandemic did not greatly affect the dispensing of the medications investigated.

• Trinh, Nhung; Houghtaling, Jared; Bernal, Fabian Leonardo Martinez; Hayati, Saeed; Maglanoc, Luigi & Lupattelli, Angela [Show all 8 contributors for this article] (2024). Harmonizing Norwegian registries onto OMOP common data model: Mapping challenges and opportunities for pregnancy and COVID-19 research. International Journal of Medical Informatics. ISSN 1386-5056. 191. doi: 10.1016/j.ijmedinf.2024.105602. Full text in Research Archive Show summary

  Objective Norwegian health registries covering entire population are used for administration, research, and emergency preparedness. We harmonized these data onto the Observational Medical Outcomes Partnership common data model (OMOP CDM) and enrich real-world data in OMOP format with COVID-19 related data. Methods Data from six registries (2018–2021) covering birth registrations, selected primary and secondary care events, vaccinations, and communicable disease notifications were mapped onto the OMOP CDM v5.3. An Extract-Transform-Load (ETL) pipeline was developed on simulated data using data characterization documents and scanning tools. We ran dashboard quality checks, cohort generations, investigated differences between source and mapped data, and refined the ETL accordingly. Results We mapped 1.5 billion rows of data of 5,673,845 individuals. Among these, there were 804,277 pregnancies, 483,585 mothers together with 792,477 children, and 472,948 fathers. We identified 382,516 positive tests for COVID-19 in 380,794 patients. These figures are consistent with results from source data. In addition to 11 million source codes mapped automatically, we mapped 237 non-standard codes to standard concepts and introduced 38 custom concepts to accommodate pregnancy-related terminologies that were not supported by OMOP CDM vocabularies. A total of 3,700/3,705 (99.8%) checks passed. The 5 failed checks could be explained by the nature of the data and only represent a small number of records. Discussion and conclusion Norwegian registry data were successfully harmonized onto OMOP CDM with high level of concordance and provides valuable source for federated COVID-19 related research. Our mapping experience is highly valuable for data partners with Nordic health registries.

• Joseph-Delaffon, Kristen; Eletri, Lina; Dechartres, Agnès; Nordeng, Hedvig Marie Egeland; Richardson, Jonathan Luke & Elefant, Elisabeth [Show all 8 contributors for this article] (2024). Neonatal outcomes after in utero exposure to antipsychotics: a systematic review and meta-analysis. European Journal of Epidemiology (EJE). ISSN 0393-2990. 39, p. 1073–1096. doi: 10.1007/s10654-024-01156-y. Full text in Research Archive
• Moreno-Martos, David; Zhao, Jing; Li, Huiqi; Nyberg, Fredrik; Bjørndal, Ludvig Daae & Hajiebrahimi, Mohammadhossein [Show all 13 contributors for this article] (2024). Impact of the early COVID-19 pandemic on adult mental health-related dispensed medications, hospitalizations and specialist outpatient visits in Norway and Sweden: Interrupted time series analysis. British Journal of Clinical Pharmacology. ISSN 0306-5251. 90(7), p. 1627–1636. doi: 10.1111/bcp.16044. Full text in Research Archive
• Nordeng, Hedvig Marie Egeland; Lupattelli, Angela; Engjom, Hilde Marie & Gelder, Marleen van (2024). Detecting and Dating Early Non-live Pregnancy Outcomes: Generation of a Novel Pregnancy Algorithm From Norwegian Linked Health Registries. Pharmacoepidemiology and Drug Safety. ISSN 1053-8569. 33(9). doi: 10.1002/pds.70002. Full text in Research Archive Show summary

  Purpose Pregnancies ending before gestational week 12 are common but not notified to the Medical Birth Registry of Norway. Our goal was to develop an algorithm that more completely detects and dates all possible pregnancy outcomes (i.e., miscarriages, elective terminations, ectopic pregnancies, molar pregnancies, stillbirths, and live births) by using diagnostic codes from primary and secondary care registries to complement information from the birth registry. Methods We used nationwide linked registry data between 2008 and 2018 in a hierarchical manner: We developed the UiO pregnancy algorithm to arrive at unique pregnancy outcomes, considering codes within 56 days as the same event. To estimate the gestational age of pregnancy outcomes identified in the primary and secondary care registries, we inferred the median gestational age of pregnancy markers (45 ICD-10 codes and 9 ICPC-2 codes) from pregnancies registered in the medical birth registry. When no pregnancy markers were available, we assigned outcome-specific gestational age estimates. The performance of the algorithm was assessed by blinded clinicians. Results Using only the medical birth registry, we identified 649 703 pregnancies, including 1369 (0.2%) miscarriages and 3058 (0.5%) elective terminations. With the new algorithm, we detected 859 449 pregnancies, including 642 712 live-births (74.8%), 112 257 miscarriages (13.1%), 94 664 elective terminations (11.0%), 6429 ectopic pregnancies (0.7%), 2564 stillbirths (0.3%), and 823 molar pregnancies (0.1%). The median gestational age was 10+1 weeks (IQR 10+0–12+2) for miscarriages and 8+0 weeks (IQR 8+0–9+6) for elective terminations. Gestational age could be inferred using pregnancy markers for 66.3% of miscarriages and 47.2% of elective terminations. Conclusion The UiO pregnancy algorithm improved the detection and dating of early non-live pregnancy outcomes that would have gone unnoticed if relying solely on the medical birth registry information.

• Noh, Yunha; Jeong, Han Eol; Choi, Ahhyung; Choi, Eun-Young; Pasternak, Björn & Nordeng, Hedvig Marie Egeland [Show all 11 contributors for this article] (2023). Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children. JAMA pediatrics. ISSN 2168-6203. 177(3), p. 267–277. doi: 10.1001/jamapediatrics.2022.5193. Full text in Research Archive
• Lupattelli, Angela; Trinh, Nhung & Nordeng, Hedvig Marie Egeland (2023). Association of maternal personality traits with medication use during pregnancy to appraise unmeasured confounding in long-term pharmacoepidemiological safety studies. Frontiers in Pharmacology. 14. doi: 10.3389/fphar.2023.1160168. Full text in Research Archive Show summary

  Maternal personality is a possible confounder on the association between prenatal medication exposure and long-term developmental outcomes in offspring, but it is often unmeasured. This study aimed to (i) estimate the association between five maternal personality traits and prenatal use of acetaminophen (including extended use), opioid analgesics, antidepressants, benzodiazepines/z-hypnotics, and antipsychotics; (ii) evaluate, using an applied example, whether unmeasured confounding by maternal neuroticism would make the association between prenatal antidepressant-child ADHD null, using the E-value framework. We used data from 8,879 pregnant women and recent mothers who participated in the Multinational Medication Use in Pregnancy Study, a web-based cross-sectional study performed within the period from 1-Oct-2011 to 29-Feb-2012 in Europe, North America and Australia. Medication use in pregnancy was self-reported by the women. Personality was assessed with the Big Five Inventory, capturing the dimensions of neuroticism, extraversion, openness, agreeableness, and conscientiousness. Adjusted logistic regression analyses were conducted for each trait-medication pair, using the survey weighting. There was a strong association between having high neuroticism and prenatal use of antidepressants (Odds Ratio (OR): 5.63, 95% Confidence Interval (CI): 3.96-8.01), benzodiazepines/z-hypnotics (OR: 6.66, 95% CI: 4.05-10.95), and analgesic opioids (OR: 2.24, 95% CI: 1.41-3.56), but not with antipsychotics. Among women with mental illness, this association attenuated for benzodiazepines/z-hypnotics, but decreased to the null for antidepressants. High neuroticism (OR: 1.31, 95% CI: 1.08-1.59) and high openness (OR: 0.77, 95% CI: 0.64-0.93) were associated with extended use of acetaminophen. The E-value for the Hazard Ratio 1.93 in the applied example was 3.27. If the example study was conducted using a population comparison group, high maternal neuroticism could have explained away the association antidepressant-ADHD. Because the example study included only women with a mental illness, this risk of bias was assessed as minimal. Various personality dispositions in the mother are associated, with a different degree, to prenatal use of medication. The strength of these association can aid researchers in evaluating the influence of uncontrolled confounding by maternal personality in long-term safety studies in pregnancy, using the E-value. This assessment should always be performed in addition to a rigorous study design using approaches to triangulate the evidence.

• Maisonneuve, Emeline; Gerbier, Eva; Tauqeer, Fatima; Pomar, Léo; Favre, Guillaume & Winterfeld, Ursula [Show all 12 contributors for this article] (2023). Determinants of Vaccination and Willingness to Vaccinate against COVID-19 among Pregnant and Postpartum Women during the Third Wave of the Pandemic: A European Multinational Cross-Sectional Survey. Viruses. 15(5). doi: 10.3390/v15051090. Full text in Research Archive Show summary

  With COVID-19 vaccination hesitancy at around 50% in the obstetric population, it is critical to identify which women should be addressed and how. Our study aimed to assess COVID-19 vaccination willingness among pregnant and postpartum women in Europe and to investigate associated determinants. This study was a cross-sectional, web-based survey conducted in Belgium, Norway, Switzerland, The Netherlands, and United Kingdom (UK) in June–August 2021. Among 3194 pregnant women, the proportions of women vaccinated or willing to be vaccinated ranged from 80.5% in Belgium to 21.5% in Norway. The associated characteristics were country of residence, chronic illness, history of flu vaccine, trimester of pregnancy, belief that COVID-19 is more severe during pregnancy, and belief that the COVID-19 vaccine is effective and safe during pregnancy. Among 1659 postpartum women, the proportions of women vaccinated or willing to be vaccinated ranged from 86.0% in the UK to 58.6% in Switzerland. The associated determinants were country of residence, chronic illness, history of flu vaccine, breastfeeding, and belief that the COVID-19 vaccine is safe during breastfeeding. Vaccine hesitancy in the obstetric population depends on medical history and especially on the opinion that the vaccine is safe and on the country of residence.

• Cardoso, Evelina; Guidi, Monia; Nauwelaerts, Nina; Nordeng, Hedvig Marie Egeland; Teil, Marie & Allegaert, Karel [Show all 12 contributors for this article] (2023). Safety of medicines during breastfeeding–from case report to modeling: a contribution from the ConcePTION project. Expert Opinion on Drug Metabolism & Toxicology. ISSN 1742-5255. 19(5), p. 269–283. doi: 10.1080/17425255.2023.2221847. Full text in Research Archive
• Monfort, Anaëlle; Cardoso, Evelina; Eap, Chin B.; Fumeaux, Céline J. Fischer; Graz, Myriam Bickle & Harari, Mathilde Morisod [Show all 17 contributors for this article] (2023). Infant exposure to Fluvoxamine through placenta and human milk: a case series - A contribution from the ConcePTION project. Frontiers in Psychiatry. 14, p. 1–6. doi: 10.3389/fpsyt.2023.1167870. Full text in Research Archive Show summary

  Introduction Fluvoxamine is widely used to treat depression during pregnancy and lactation. However, limited data are available on its transfer to the fetus or in human milk. This case series provides additional information on the infant exposure to fluvoxamine during pregnancy and lactation. Case presentation Two women, aged 38 and 34 years, diagnosed with depression were treated with 50 mg fluvoxamine during pregnancy and lactation. At delivery a paired maternal and cord blood sample was collected for each woman. The first mother exclusively breastfed her child for 4 months and gave one foremilk and one hindmilk sample at 2 days and 4 weeks post-partum, whereas the second mother did not breastfeed. Results The cord to plasma concentration ratios were 0.62 and 0.48, respectively. At 2 weeks post-partum, relative infant doses (RID) were 0.47 and 0.57% based on fluvoxamine concentrations in foremilk and hindmilk, respectively. At 4 weeks post-partum, the RIDs were 0.35 and 0.90%, respectively. The child from the first mother was born healthy and showed a normal development at the 6th, 18th and 36th month follow-ups. One of the twins from the second woman was hospitalized for hypoglycemia that was attributed to gestational diabetes and low birth weight. The second one was born healthy. Conclusion These results suggest a minimal exposure to fluvoxamine during lactation which is in accordance with previously published data. Larger clinical and pharmacokinetic studies assessing the long-term safety of this drug during lactation and the variability of its exposure through breastmilk are warranted.

• Olstad, Emilie Willoch; Nordeng, Hedvig Marie Egeland; Sandve, Geir Kjetil Ferkingstad; Lyle, Robert & Gervin, Kristina (2023). Effects of prenatal exposure to (es)citalopram and maternal depression during pregnancy on DNA methylation and child neurodevelopment. Translational Psychiatry. 13(1). doi: 10.1038/s41398-023-02441-2. Full text in Research Archive Show summary

  Abstract Studies assessing associations between prenatal exposure to antidepressants, maternal depression, and offspring DNA methylation (DNAm) have been inconsistent. Here, we investigated whether prenatal exposure to citalopram or escitalopram ((es)citalopram) and maternal depression is associated with differences in DNAm. Then, we examined if there is an interaction effect of (es)citalopram exposure and DNAm on offspring neurodevelopmental outcomes. Finally, we investigated whether DNAm at birth correlates with neurodevelopmental trajectories in childhood. We analyzed DNAm in cord blood from the Norwegian Mother, Father and Child Cohort Study (MoBa) biobank. MoBa contains questionnaire data on maternal (es)citalopram use and depression during pregnancy and information about child neurodevelopmental outcomes assessed by internationally recognized psychometric tests. In addition, we retrieved ADHD diagnoses from the Norwegian Patient Registry and information on pregnancies from the Medical Birth Registry of Norway. In total, 958 newborn cord blood samples were divided into three groups: (1) prenatal (es)citalopram exposed ( n  = 306), (2) prenatal maternal depression exposed ( n  = 308), and (3) propensity score-selected controls ( n  = 344). Among children exposed to (es)citalopram, there were more ADHD diagnoses and symptoms and delayed communication and psychomotor development. We did not identify differential DNAm associated with (es)citalopram or depression, nor any interaction effects on neurodevelopmental outcomes throughout childhood. Trajectory modeling identified subgroups of children following similar developmental patterns. Some of these subgroups were enriched for children exposed to maternal depression, and some subgroups were associated with differences in DNAm at birth. Interestingly, several of the differentially methylated genes are involved in neuronal processes and development. These results suggest DNAm as a potential predictive molecular marker of later abnormal neurodevelopmental outcomes, but we cannot conclude whether DNAm links prenatal (es)citalopram exposure or maternal depression with child neurodevelopmental outcomes.

• Shakibfar, Saeed; Nyberg, Fredrik; Li, Huiqi; Zhao, Jing; Nordeng, Hedvig Marie Egeland & Sandve, Geir Kjetil Ferkingstad [Show all 10 contributors for this article] (2023). Artificial intelligence-driven prediction of COVID-19-related hospitalization and death: a systematic review. Frontiers in Public Health. 11. doi: 10.3389/fpubh.2023.1183725. Full text in Research Archive Show summary

  Aim To perform a systematic review on the use of Artificial Intelligence (AI) techniques for predicting COVID-19 hospitalization and mortality using primary and secondary data sources. Study eligibility criteria Cohort, clinical trials, meta-analyses, and observational studies investigating COVID-19 hospitalization or mortality using artificial intelligence techniques were eligible. Articles without a full text available in the English language were excluded. Data sources Articles recorded in Ovid MEDLINE from 01/01/2019 to 22/08/2022 were screened. Data extraction We extracted information on data sources, AI models, and epidemiological aspects of retrieved studies. Bias assessment A bias assessment of AI models was done using PROBAST. Participants Patients tested positive for COVID-19. Results We included 39 studies related to AI-based prediction of hospitalization and death related to COVID-19. The articles were published in the period 2019-2022, and mostly used Random Forest as the model with the best performance. AI models were trained using cohorts of individuals sampled from populations of European and non-European countries, mostly with cohort sample size &amp;lt;5,000. Data collection generally included information on demographics, clinical records, laboratory results, and pharmacological treatments (i.e., high-dimensional datasets). In most studies, the models were internally validated with cross-validation, but the majority of studies lacked external validation and calibration. Covariates were not prioritized using ensemble approaches in most of the studies, however, models still showed moderately good performances with Area under the Receiver operating characteristic Curve (AUC) values &amp;gt;0.7. According to the assessment with PROBAST, all models had a high risk of bias and/or concern regarding applicability. Conclusions A broad range of AI techniques have been used to predict COVID-19 hospitalization and mortality. The studies reported good prediction performance of AI models, however, high risk of bias and/or concern regarding applicability were detected.

• Spildrejorde, Mari; Samara, Athina; Sharma, Ankush; Leithaug, Magnus; Falck, Martin Bengt Alfred & Modafferi, Stefania [Show all 12 contributors for this article] (2023). Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol. iScience. 26:107755(10), p. 1–29. doi: 10.1016/j.isci.2023.107755. Full text in Research Archive Show summary

  Prenatal paracetamol exposure has been associated with neurodevelopmental outcomes in childhood. Pharmacoepigenetic studies show differences in cord blood DNA methylation between unexposed and paracetamol-exposed neonates, however, causality and impact of long-term prenatal paracetamol exposure on brain development remain unclear. Using a multi-omics approach, we investigated the effects of paracetamol on an in vitro model of early human neurodevelopment. We exposed human embryonic stem cells undergoing neuronal differentiation with paracetamol concentrations corresponding to maternal therapeutic doses. Single-cell RNA-seq and ATAC-seq integration identified paracetamol-induced chromatin opening changes linked to gene expression. Differentially methylated and/or expressed genes were involved in neurotransmission and cell fate determination trajectories. Some genes involved in neuronal injury and development-specific pathways, such as KCNE3, overlapped with differentially methylated genes previously identified in cord blood associated with prenatal paracetamol exposure. Our data suggest that paracetamol may play a causal role in impaired neurodevelopment.

• Bromley, Rebecca; Graz, Myriam Bickle; Bluett-Duncan, Matthew; Chambers, C.; Damkier, P. & Dietrich, K. [Show all 26 contributors for this article] (2023). Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies. Frontiers in Pharmacology. 14. doi: 10.3389/fphar.2023.1094698. Full text in Research Archive Show summary

  Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero . Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance.

• Maisonneuve, Emeline; Bruin, Odette de; Favre, Guillaume; Goncé, Anna; Donati, Serena & Engjom, Hilde Marie [Show all 14 contributors for this article] (2023). Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020–2022: A Scoping Review. Journal of Clinical Medicine. 12(13). doi: 10.3390/jcm12134519. Full text in Research Archive Show summary

  The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists’ societies in thirteen countries in 2020–2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir–ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir–ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19.

• Cardoso, Evelina; Monfort, Anaëlle; Ferreira, Ema; Nordeng, Hedvig Marie Egeland; Winterfeld, Ursula & Allegaert, Karel [Show all 9 contributors for this article] (2023). Maternal drugs and breastfeeding: Risk assessment from pharmacokinetics to safety evidence - A contribution from the ConcePTION project. The´rapie (Paris). ISSN 0040-5957. 78(2), p. 149–156. doi: 10.1016/j.therap.2023.01.008. Full text in Research Archive Show summary

  Human milk is the most appropriate form of nutrition for infants while taking medication during the postpartum period is common. Discontinuation of breastfeeding is sometimes wrongly recommended for fear of adverse effects in the breastfed infant whereas only a few drugs are strictly contraindicated while breastfeeding. Most drugs are transferred from the mother's blood to the milk, but the breastfed infant usually ingests a small drug amount through human milk. As population-based evidence is still scarce on safety of drugs during breastfeeding, risk assessment relies on the little clinical evidence available and on pharmacokinetic principles, as well as on specialized sources of information that are essential for clinical decision-making. Risk assessment should not only be based on the drug's potential risk for the breastfed infant but should always take into account the benefits associated to breastfeeding, the risks of untreated maternal disease and the maternal willingness to breastfeed. Identifying situations with potential for drug accumulation in the breastfed infant is decisive while assessing the risk. Health care providers should always assume that mothers will be concerned and use risk communication as a key to ensure medication adherence and prevent unnecessary interruption of breastfeeding. When a mother still expresses concerns, decision support algorithms may facilitate communication and some strategies can be offered to minimize the drug exposure in the breastfed infant even when clinically not justified.

• Trinh, Nhung; Munk-Olsen, Trine; Wray, Naomi R.; Bergink, Veerle; Nordeng, Hedvig Marie Egeland & Lupattelli, Angela [Show all 7 contributors for this article] (2023). Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway. JAMA psychiatry. ISSN 2168-6238. 80(5), p. 441–450. doi: 10.1001/jamapsychiatry.2023.0041. Full text in Research Archive
• Nordeng, Hedvig Marie Egeland; Wegler, Christine; Lindqvist, Annika; Melander, Erik; Magnusson, Mikaela & Gandia, Peggy [Show all 9 contributors for this article] (2023). Transfer of cetirizine/levocetirizine into human breast milk and estimation of drug exposure to infants through breastfeeding: A human lactation study from the ConcePTION project. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 134(1), p. 153–164. doi: 10.1111/bcpt.13948. Full text in Research Archive Show summary

  Data on drug transfer into human breast milk are sparse. This study aimed to quantify concentrations of cetirizine and levocetirizine in breast milk and to estimate drug exposure to infants. Breastfeeding women at least 8 weeks postpartum and using cetirizine or its pure (R)-enantiomer levocetirizine were eligible to participate. Breast milk samples were collected at six predefined times during a dose interval (0, 2, 4, 8, 12 and 24 h after drug intake) at steady state. Infant drug exposure was estimated by calculating the absolute infant dose (AID) and the weight-adjusted relative infant dose (RID). In total, 32 women were eligible for final inclusion, 31 women using cetirizine and one woman using levocetirizine. Means of the individual maximum and average cetirizine milk concentrations were 41.0 and 16.8 μg/L, respectively. Maximum concentrations occurred on average 2.4 h after intake, and the mean half-life in milk was 7.0 h. Estimated AID and RID for cetirizine in a day were 2.5 μg/kg and 1.9%, respectively. The corresponding values for levocetirizine were 1.1 μg/kg and 1.9%. No severe adverse events were reported. Our findings demonstrate that the transfer of cetirizine and levocetirizine into breast milk is low and compatible with breastfeeding.

• Ngo, Elin Thuy Phuong; Truong, Maria Bich-Thuy & Nordeng, Hedvig Marie Egeland (2023). Impact of a primary care pharmacist consultations on pregnant women’s medication use: the SafeStart intervention study linked to a national prescription database. International Journal of Clinical Pharmacy. ISSN 2210-7703. 45, p. 893–902. doi: 10.1007/s11096-023-01577-x. Full text in Research Archive Show summary

  Abstract Background Prior studies show that pharmacist consultations are highly appreciated by pregnant women and feasible in community pharmacies. However, it is unknown whether such counseling has an impact on medication use during pregnancy. Aim This study aimed to assess whether a pharmacist consultation in early pregnancy was associated with pregnant women’s medication use, with a focus on antiemetic medications. Method The SafeStart study recruited Norwegian pregnant women in the first trimester between February 2018 and February 2019. Women in the intervention group received a pharmacist consultation in a community pharmacy or by phone. A follow-up questionnaire was completed 13 weeks after enrollment. Data from the SafeStart study were linked to the Norwegian Prescription Database. Logistic regression was used to assess the association between the pharmacist intervention and medication use in the second trimester. Results The study included 103 women in the intervention group and 126 in the control group. Overall prescription fills in the first and second trimesters were 55% and 45% (intervention group) and 49% and 52% (control group), respectively. In total, 16–20% of women in the first trimester and 21–27% of women in the second trimester had a prescription for antiemetics. The pharmacist intervention was not associated with women’s medication use in the second trimester. Conclusion This study did not detect an impact of a pharmacist consultation on pregnant women’s use of medications. In the future, pharmacist consultations should focus on other outcome factors, such as risk perception, knowledge level, and the use of other health care services. Trial registration The SafeStart study is registered with ClinicalTrials.gov (identifier: NCT04182750, registration date: December 2, 2019).

• Shakibfar, Saeed; Zhao, Jing; Li, Huiqi; Nordeng, Hedvig Marie Egeland; Lupattelli, Angela & Pavlović, Milena [Show all 12 contributors for this article] (2023). Machine learning-driven development of a disease risk score for COVID-19 hospitalization and mortality: a Swedish and Norwegian register-based study. Frontiers in Public Health. 11. doi: 10.3389/fpubh.2023.1258840. Full text in Research Archive Show summary

  Aims To develop a disease risk score for COVID-19-related hospitalization and mortality in Sweden and externally validate it in Norway. Method We employed linked data from the national health registries of Sweden and Norway to conduct our study. We focused on individuals in Sweden with confirmed SARS-CoV-2 infection through RT-PCR testing up to August 2022 as our study cohort. Within this group, we identified hospitalized cases as those who were admitted to the hospital within 14 days of testing positive for SARS-CoV-2 and matched them with five controls from the same cohort who were not hospitalized due to SARS-CoV-2. Additionally, we identified individuals who died within 30 days after being hospitalized for COVID-19. To develop our disease risk scores, we considered various factors, including demographics, infectious, somatic, and mental health conditions, recorded diagnoses, and pharmacological treatments. We also conducted age-specific analyses and assessed model performance through 5-fold cross-validation. Finally, we performed external validation using data from the Norwegian population with COVID-19 up to December 2021. Results During the study period, a total of 124,560 individuals in Sweden were hospitalized, and 15,877 individuals died within 30 days following COVID-19 hospitalization. Disease risk scores for both hospitalization and mortality demonstrated predictive capabilities with ROC-AUC values of 0.70 and 0.72, respectively, across the entire study period. Notably, these scores exhibited a positive correlation with the likelihood of hospitalization or death. In the external validation using data from the Norwegian COVID-19 population (consisting of 53,744 individuals), the disease risk score predicted hospitalization with an AUC of 0.47 and death with an AUC of 0.74. Conclusion The disease risk score showed moderately good performance to predict COVID-19-related mortality but performed poorly in predicting hospitalization when externally validated.

• Olstad, Emilie Willoch; Nordeng, Hedvig Marie Egeland; Lyle, Robert & Gervin, Kristina (2023). No impact of prenatal paracetamol and folic acid exposure on cord blood DNA methylation in children with attention-deficit/hyperactivity disorder. Frontiers in Genetics. 14, p. 1–6. doi: 10.3389/fgene.2023.1204879. Full text in Research Archive Show summary

  Pharmacoepigenetic studies are important to understand the mechanisms through which medications influence the developing fetus. For instance, we and others have reported associations between prenatal paracetamol exposure and offspring DNA methylation (DNAm). Additionally, folic acid (FA) intake during pregnancy has been associated with DNAm in genes linked to developmental abnormalities. In this study, we aimed to: (i) expand on our previous findings showing differential DNAm associated with long-term prenatal paracetamol exposure in offspring with attention-deficit/hyperactivity disorder (ADHD), and (ii) examine if there is an interaction effect of FA and paracetamol on DNAm in children with ADHD. We used data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). We did not identify any impact of paracetamol or any interaction effect of paracetamol and FA on cord blood DNAm in children with ADHD. Our results contribute to the growing literature on prenatal pharmacoepigenetics, but should be replicated in other cohorts. Replication of pharmacoepigenetic studies is essential to ensure robust findings and to increase the clinical relevance of such studies.

• Gelder, Marleen van; Lupattelli, Angela & Nordeng, Hedvig Marie Egeland (2023). Risk of spontaneous abortion after periconceptional medication use: Time to tackle the methodological challenges. Paediatric and Perinatal Epidemiology. ISSN 0269-5022. doi: 10.1111/ppe.12967. Full text in Research Archive
• Tauqeer, Fatima; Ceulemans, Michael; Gerbier, Eva; Passier, Anneke; Oliver, Alison & Foulon, Veerle [Show all 9 contributors for this article] (2023). Mental health of pregnant and postpartum women during the third wave of the COVID-19 pandemic: a European cross-sectional study. BMJ Open. 13(1). doi: 10.1136/bmjopen-2022-063391. Full text in Research Archive Show summary

  Objective: To describe the mental health of perinatal women in five European countries during the third pandemic wave and identify risk factors related to depressive and anxiety symptoms. Design: A cross-sectional, online survey-based study. Setting: Belgium, Norway, Switzerland, the Netherlands and the UK, 10 June 2021-22 August 2021. Participants: Pregnant and up to 3 months postpartum women, older than 18 years of age. Primary outcome measure: The Edinburgh Depression Scale (EDS) and the Generalised Anxiety Disorder scale (GAD-7) were used to assess mental health status. Univariate and multivariate generalised linear models were performed to identify factors associated with poor mental health. Results: 5210 women participated (including 3411 pregnant and 1799 postpartum women). The prevalence of major depressive symptoms (EDS ≥13) was 16.1% in the pregnancy group and 17.0% in the postpartum . Moderate to severe generalised anxiety symptoms (GAD ≥10) were found among 17.3% of the pregnant and 17.7% of the postpartum women. Risk factors associated with poor mental health included having a pre-existing mental illness, a chronic somatic illness, having had COVID-19 or its symptoms, smoking, unplanned pregnancy and country of residence. Among COVID-19 restrictive measures specific to perinatal care, pregnant and postpartum women were most anxious about not having their partner present at the time of delivery, that their partner had to leave the hospital early and to be separated from their newborn after the delivery. Conclusion: Approximately one in six pregnant or postpartum women reported major depression or anxiety symptoms during the third wave of the pandemic. These findings suggest a continued need to monitor depression and anxiety in pregnancy and postpartum populations throughout and in the wake of the pandemic. Tailored support and counseling are essential to reduce the burden of the pandemic on perinatal and infant mental health.

• Araya, Robin Aasegg; Tauqeer, Fatima; Ceulemans, Michael; Gerbier, Eva; Maisonneuve, Emeline & Passier, Anneke [Show all 10 contributors for this article] (2023). Pregnancy- and Birth-Related Experiences among Postpartum Women during the Third Wave of the COVID-19 Pandemic—A Multinational European Study. Pharmacoepidemiology. 2(1), p. 54–67. doi: 10.3390/pharma2010006. Full text in Research Archive Show summary

  The objective of this study was to describe pregnancy- and birth-related experiences of postpartum women during the third wave of the COVID-19 pandemic and their association with mental health outcomes. An online questionnaire was distributed in five European countries (Belgium, The Netherlands, Norway, Switzerland, UK) between June and August 2021. Participants were recruited though socialmedia platforms including pregnancy- and motherhood-related websites, pregnancy fora, and apps. Postpartum women were asked eleven specific questions about pregnancyand birth-related changes and the presence of support during delivery. The Edinburgh Depression Scale was used to assess depressive and anxiety symptoms. Covariates included sociodemographics, health and reproductive characteristics, and COVID-19 status. Associations were estimated with logistic regression. The study included 1730 postpartum women. Frequent changes included the exclusion of the partner from pregnancy care appointments (83.2%), changed prenatal care settings (64.4%), and cancellation of hospital information visits (42.7%). Few women, however, were without support apart from medical staff during delivery (1.4%). The number of pregnancy- and birth-related changes was associated with each woman’s mental health status, as well as the type of change. Experiencing changes related to delivery and cancellation or reduction of prenatal examination was associated with a doubling in the odds of symptoms of major depression and anxiety postpartum. These findings highlight the importance of ensuring adequate maternity care for women’s mental health postpartum, as well as during a pandemic.

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2022). Use of statins and other lipid-modifying agents across pregnancy: A nationwide drug utilization study in Norway in 2005–2018. Atherosclerosis. ISSN 0021-9150. p. 1–10. doi: 10.1016/j.atherosclerosis.2022.11.022. Full text in Research Archive Show summary

  Background and aims Statins are becoming more widely used among women of reproductive age; however, nationwide data on statin use across pregnancy is scarce. We therefore aimed to describe the drug utilization patterns for statins and other lipid-modifying agents (LMAs) before, during, and after pregnancy, for all pregnancies in Norway from 2005 to 2018. Methods We linked individual-level data from four nationwide electronic health care registries in Norway and characterized the prescription fills of statins and other LMAs across pregnancy. We also examined trends in pregnancy-related LMA use, and characterized women using statins and other LMAs on parameters of health status and co-morbidity. Results In total, 822,071 pregnancies for 503,723 women were included. The number of statin prescription fills decreased rapidly during the first trimester and returned to pre-pregnancy levels about one year postpartum. Pregnancy-related statin use increased from 2005 (approx. 0.11% of all pregnancies) to 2018 (approx. 0.29% of all pregnancies); however, in total, few statin prescriptions were filled within any trimester of pregnancy (n = 331, 0.04% of all pregnancies). Statin use was more common in women with higher age, higher weight, smoking, and comorbidities such as hypertension and diabetes mellitus; also, statin users often had co-medication pertinent to these conditions. Conclusions Although statins and other LMAs were increasingly being used around the time of pregnancy among women in Norway, drug use was mostly discontinued during the first trimester. Our results suggest that pregnancy-related statin use should be monitored, and that drug safety analyses for maternal and offspring health outcomes are needed.

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2022). Use of statins and other lipid-modifying agents across pregnancy – a nationwide drug utilization study of 822 071 pregnancies in Norway in 2005-2018. medRxiv. doi: 10.1101/2022.06.28.22276237. Full text in Research Archive
• Trinh, Nhung; Nordeng, Hedvig Marie Egeland; Bandoli, Gretchen; Eberhard-Gran, Malin Marie Cecilia & Lupattelli, Angela (2022). Antidepressant and mental health care utilization in pregnant women with depression and/or anxiety: An interrupted time-series analysis. Journal of Affective Disorders. ISSN 0165-0327. 308, p. 458–465. doi: 10.1016/j.jad.2022.04.101. Full text in Research Archive Show summary

  Background Little is known about mental health care utilization patterns in pregnant women with depression/anxiety in Norway according to antidepressant fill trajectories in pregnancy. Method We conducted a registry-linkage cohort study of pregnancies within women having outpatient visit for depression/anxiety and antidepressant fills prior to pregnancy identified from four national registries of Norway (2009–2018). Number of consultations for depression/anxiety per 100 pregnancies as proxy of mental health care utilization was modelled using interrupted time-series analysis with first month into pregnancy and first month after delivery as interruption points. We investigated the time window spanning from six months prior to one year postpartum. Antidepressant fill trajectories in the corresponding time window were identified using longitudinal k-means trajectory modelling. Results The cohort included 8460 pregnancies within 8062 women with depression/anxiety. We observed reduced mental health care utilization when pregnant women entered the course of pregnancy (negative slopes during pregnancy for psychiatric specialists and psychologists). The declines were observed for all antidepressant fill trajectories (i.e., discontinuers and continuers) except interrupters (i.e., discontinued then resumed treatment). We found increased mental health care utilization in the postpartum year, notably in interrupters (positive slopes in consultation rates with specialists of outpatient clinics and public-contracted psychiatrists). Limitations It was not possible to measure directly the use of psychosocial interventions and psychotherapy. Conclusions Pregnancy was associated with reduced mental health care utilization regardless of whether antidepressant treatment was maintained during pregnancy or not. Increases in mental health care utilization were observed in the postpartum year, especially in interrupters.

• Slattery, Jim; Quinten, Chantal; Candore, Gianmario; Pinheiro, Luis; Flynn, Robert & Kurz, Xavier [Show all 7 contributors for this article] (2022). Ondansetron use in nausea and vomiting during pregnancy: A descriptive analysis of prescription patterns and patient characteristics in UK general practice. British Journal of Clinical Pharmacology. ISSN 0306-5251. 88(10), p. 4526–4539. doi: 10.1111/bcp.15370. Full text in Research Archive Show summary

  Aims The objective of this study was to describe ondansetron drug utilization patterns during pregnancy to treat nausea and vomiting in pregnancy (NVP). Moreover, we aimed to describe the maternal factors associated with NVP and antiemetic use. Methods The data consist of pregnancies with a live birth(s) within an IMRD-UK registered GP practice. Descriptive statistics were used to investigate patterns of ondansetron use in pregnancy and to describe maternal characteristics associated with NVP and antiemetic drug utilization. We differentiate first- from second-line use during pregnancy using antiemetic prescription pathways. Results The dataset included 733 633 recorded complete pregnancies from 2005 to 2019. NVP diagnosis and ondansetron prescription prevalence increased from 2.7% and 0.1% in 2005 to 4.8% and 2.5% in 2019 respectively. Over the period 2015–2019, the most common oral daily dosages were 4 mg/d (8.5%), 8 mg/d (37.1%), 12 mg/d (37.5%) and between 16 and 24 mg/d (16.9%). Prescription of ondansetron was initiated during the first trimester of pregnancy in 40% of the cases and was moderately used as a first-line therapy (2.8%), but preferred choice of second-line therapy. Women with mental health disorders, asthma and/or prescribed folic acid were more likely to experience NVP and use antiemetics in pregnancy than their counterparts. Conclusion This study confirms that ondansetron is increasingly used off-label to treat NVP during pregnancy, also in the first trimester and before other prescription antiemetics have been prescribed. Several maternal comorbidities and folic acid use were more common among women experiencing NVP and using antiemetics, including ondansetron.

• Andersen, Sarah Hjorth; Pottegård, Anton; Broe, Anne; Hemmingsen, Caroline H.; Leinonen, Maarit & Hargreave, Marie [Show all 8 contributors for this article] (2022). Prenatal exposure to nitrofurantoin and risk of childhood leukaemia: A registry-based cohort study in four Nordic countries. International Journal of Epidemiology. ISSN 0300-5771. 51(3), p. 778–788. doi: 10.1093/ije/dyab219. Full text in Research Archive Show summary

  Abstract Background Studies have suggested increased risks of childhood leukaemia after prenatal exposure to antibiotics, particularly nitrofurantoin. However, these findings may be related to the underlying maternal infection. This multinational study aimed to investigate the association between prenatal nitrofurantoin exposure and childhood leukaemia while accounting for maternal infection. Methods In a population-based cohort study of children born in Denmark, Finland, Norway or Sweden from 1997 to 2013, prenatal exposure to nitrofurantoin or pivmecillinam (active comparator) was ascertained from national Prescription Registries. Childhood leukaemia was identified by linkage to national Cancer Registries. Poisson regression was used to estimate incidence rate ratios (IRRs) and incidence rate differences (IRDs) with inverse probability of treatment weights applied to account for confounding. Results We included 44 091 children prenatally exposed to nitrofurantoin and 247 306 children prenatally exposed to pivmecillinam. The children were followed for 9.3 years on average (standard deviation 4.1). There were 161 cases of childhood leukaemia. The weighted IRR for prenatal nitrofurantoin exposure when compared with pivmecillinam was 1.34 (95% confidence interval 0.88, 2.06), corresponding to an IRD of 15 per million person-years. Higher point estimates were seen for first- and third-trimester exposure. There was no evidence of a dose–response relationship. Conclusions Prenatal exposure to nitrofurantoin was not substantially associated with childhood leukaemia, although a slightly elevated IRR with confidence intervals including the null was observed, corresponding to a small absolute risk. The lack of a dose–response relationship and a clear biological mechanism to explain the findings suggests against a causal association.

• Wegler, Christine; Saleh, Aljona; Lindqvist, Annika; Nordeng, Hedvig Marie Egeland; Smeraglia, John & Baranczewski, Pawel (2022). Simple and rapid quantification of cetirizine, venlafaxine, and O-desmethylvenlafaxine in human breast milk, and metformin in human milk and plasma with UHPLC-MS/MS. Journal of chromatography. B. ISSN 1570-0232. 1205. doi: 10.1016/j.jchromb.2022.123340. Full text in Research Archive
• Gerbier, Eva; Favre, Guillaume; Tauqeer, Fatima; Winterfeld, Ursula; Stojanov, Milos & Oliver, Alison [Show all 13 contributors for this article] (2022). Self-Reported Medication Use among Pregnant and Postpartum Women during the Third Wave of the COVID-19 Pandemic: A European Multinational Cross-Sectional Study. International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 19(9), p. 1–16. doi: 10.3390/ijerph19095335. Full text in Research Archive Show summary

  Information on medication utilization among pregnant and postpartum women during the pandemic is lacking. We described the prevalence and patterns of self-reported medication use among pregnant and postpartum women during the third wave of the pandemic (June–August 2021). An online questionnaire was distributed in five European countries between June–August 2021. Pregnant women or women who had delivered in the three preceding months, and ≥18 years old, could participate. The prevalence of overall medication use, self-medication, and changes in chronic medication use were determined. A total of 2158 women out of 5210 participants (41.4%) used at least one medication. Analgesics (paracetamol), systemic antihistamines (cetirizine), and drugs for gastric disorders (omeprazole) were the three most used classes. Anti-infectives were less prevalent than during pre-pandemic times. Antidepressants and anxiety related medication use remained similar, despite a higher prevalence of these symptoms. Self-medication was reported in 19.4% of women, and 4.1% of chronic medication users reported that they changed a chronic medication on personal initiative due to the pandemic. In conclusion, medication use patterns in our cohort were mostly similar to those of the first COVID-19 wave and the pre-pandemic period. More studies are needed to explore factors associated with self-medication and changes in chronic medication use due to the pandemic in this perinatal population.

• Harris, Gerd Marie Eskerud; Wood, Mollie; Ystrøm, Eivind & Nordeng, Hedvig Marie Egeland (2022). Association of Maternal Use of Triptans during Pregnancy with Risk of Attention-Deficit/Hyperactivity Disorder in Offspring. JAMA Network Open. 5(6). doi: 10.1001/jamanetworkopen.2022.15333. Full text in Research Archive Show summary

  Importance Triptans are commonly used in the treatment of migraine. Prenatal exposure to triptans may be associated with adverse fetal neurodevelopment; however, there is limited information about the long-term safety of triptan use during pregnancy. Objective To examine the association between maternal use of triptans during pregnancy and diagnosis and symptoms of attention-deficit/hyperactivity disorder (ADHD) among offspring. Design, Setting, and Participants This study used data from the Norwegian Mother, Father and Child Cohort Study (recruitment 1999-2008), linked to national health registries. Live-born singleton children born to women with migraine before or during pregnancy were included. Two analytic samples were defined: one to assess ADHD diagnosis and one to assess ADHD symptoms. Data were analyzed from May 1 to November 30, 2021. Exposure Maternal self-report of triptan use during pregnancy. Exposed children were compared with 2 groups of unexposed children whose mothers reported migraine (1) during pregnancy and (2) before pregnancy only. Main Outcomes and Measures An ADHD diagnosis was defined as diagnosis of hyperkinetic disorder or receipt of dispensed ADHD medication. Symptoms of ADHD at 5 years were measured by the Conners’ Parent Rating Scale, where a higher score indicates more symptoms of ADHD. Cox proportional hazards regression models and generalized linear models with inverse probability weights were used to estimate weighted hazard ratios (HRs) and standardized mean differences, respectively, with 95% CIs. Results The ADHD diagnosis sample comprised 10 167 children (mean [SD] maternal age, 30.2 [4.6] years; 5231 boys [51.5%]), and the ADHD symptoms sample comprised 4367 children (mean [SD] maternal age, 30.6 [4.4] years; 2191 boys [50.2%]). Children were followed up for a mean (SD) of 10.6 (2.2) years. Children with prenatal triptan exposure had no increased risk of ADHD diagnosis compared with unexposed children whose mothers had migraine during pregnancy (weighted HR, 1.16; 95% CI, 0.78-1.74) and compared with unexposed children whose mothers had migraine only before pregnancy (weighted HR, 1.28; 95% CI, 0.84-1.94). There were no differences in ADHD symptom scores between exposed and unexposed children. Conclusions and Relevance The findings of this study suggest that there is no increased risk of ADHD among offspring associated with prenatal exposure to triptans.

• Grzeskowiak, Luke E.; Saha, Moni R.; Nordeng, Hedvig Marie Egeland; Ystrøm, Eivind & Amir, Lisa H. (2022). Perinatal antidepressant use and breastfeeding outcomes: Findings from the Norwegian Mother, Father and Child Cohort Study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 101(3), p. 344–354. doi: 10.1111/aogs.14324. Full text in Research Archive Show summary

  Introduction Antidepressant use is common in the perinatal period, but there are concerns that it can negatively impact on breastfeeding outcomes. The aim of this study was to examine the effects of perinatal antidepressant use on breastfeeding initiation and duration. Material and methods This was a retrospective analysis of 80 882 mother–infant dyads in the Norwegian Mother, Father and Child Cohort Study (MoBa). Women were first classified according to self-reported mental disorders and timing of antidepressant use before and/or after gestational week 28 (i.e., early-mid–gestation and/or late-gestation use). We subsequently classified women according to self-reported mental disorders and antidepressant use postpartum and whether antidepressants were continued from late gestation or were new/restarted. Breastfeeding outcomes included breastfeeding initiation as well as predominant or any breastfeeding and abrupt breastfeeding discontinuation until 6 months. Results Late-gestation antidepressant use was associated with a reduced likelihood of breastfeeding initiation (adjusted relative risk [aRR] 0.93; 95% confidence interval [CI] 0.90–0.97) but not predominant (aRR 0.96; 95% CI 0.67–1.39) or any (aRR 1.00; 95% CI 0.93–1.07) breastfeeding at 6 months compared with unexposed women with mental disorders. When examined according to postnatal antidepressant use, no differences in predominant (aRR 0.94; 95% CI 0.60–1.48) or any breastfeeding (aRR 0.99; 95% CI 0.91–1.07) at 6 months were evident among women who continued antidepressant use from late gestation into the postpartum period compared with unexposed women with mental disorders. In contrast, new/restarted antidepressant use postpartum was associated with a reduced likelihood of predominant (aRR 0.37; 95% CI 0.22–0.61) and any (aRR 0.49; 95% CI 0.42–0.56) breastfeeding at 6 months, as well as increased risk of abrupt breastfeeding discontinuation (aRR 2.64; 95% CI 2.07–3.37) compared with the unexposed women with mental disorders. Conclusions A complex relation exists between depression, antidepressant use, and breastfeeding outcomes. Antidepressant use in late pregnancy was associated with a reduced likelihood of breastfeeding initiation but not breastfeeding duration or exclusivity. In contrast, initiating or restarting antidepressants postpartum was associated with poorer breastfeeding outcomes. Overall, women taking antidepressants and women with a mental disorder may benefit from additional education and support to improve breastfeeding rates and promote maternal and infant health and wellbeing.

• Thurin, Nicolas H.; Pajouheshnia, Romin; Roberto, Giuseppe; Dodd, Caitlin; Hyeraci, Giulia & Bartolini, Claudia [Show all 42 contributors for this article] (2022). From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding. Clinical Pharmacology and Therapeutics. ISSN 0009-9236. 111(1), p. 321–331. doi: 10.1002/cpt.2476. Full text in Research Archive
• Trinh, Nhung; Nordeng, Hedvig Marie Egeland; Bandoli, Gretchen; Palmsten, Kristin; Eberhard-Gran, Malin & Lupattelli, Angela (2022). Antidepressant Fill and Dose Trajectories in Pregnant Women with Depression and/or Anxiety: A Norwegian Registry Linkage Study. Clinical Epidemiology. 14, p. 1439–1451. doi: 10.2147/CLEP.S379370. Full text in Research Archive Show summary

  Background: Few studies investigated longitudinal antidepressant exposure during pregnancy and included dosage in the assessment. Methods: We conducted a nationwide, registry-linkage study in Norway using data on antidepressant prescription fills in pregnancies lasting ≥ 32 weeks in women with a delivery between 2009 and 2018 who had a depression/anxiety diagnosis and antidepressant fills prior to pregnancy. Information on antidepressant exposure by week (measured by filled prescriptions) and prescribed average daily dose was used in longitudinal k-means trajectory modelling for a 108-week time window from six months prior to pregnancy to one year after delivery. Factors associated with trajectory group membership were examined using multinomial logistic regression models. Results: We included 8,460 pregnancies in 8,092 women. Four antidepressant fill trajectories were identified based on filled antidepressant prescriptions: two distinct discontinuing patterns, one at around the start of pregnancy (30.4%) and one around the end of pregnancy (33.8%); one continuing pattern (20.6%); and one interrupting pattern (15.2%). Using average usual daily dose, we identified low dose discontinuing (60.3%), medium dose reducing (20.6%) and high dose continuing (15.2%) patterns. The multinomial logistic regressions showed that the fill trajectory group membership was strongly associated with: antidepressant type and dose prior to pregnancy and co-medication prior to pregnancy, maternal age, marital status, parity, previous pregnancy loss, and pregnancy planning. Conclusion: Longitudinal trajectory modelling revealed distinct antidepressant fill and dosage patterns in the period around pregnancy. Knowledge about factors associated with utilization trajectories might be useful for health-care personnel counselling women about antidepressant use in pregnancy.

• Ngo, Elin Thuy Phuong; Truong, Maria Bich-Thuy; Wright, David John & Nordeng, Hedvig Marie Egeland (2022). Impact of a Mobile Application for Tracking Nausea and Vomiting During Pregnancy (NVP) on NVP Symptoms, Quality of Life, and Decisional Conflict Regarding NVP Treatments: MinSafeStart Randomized Controlled Trial. JMIR mhealth and uhealth. 10(7). doi: 10.2196/36226. Full text in Research Archive Show summary

  Background: Pregnant women are active users of mobile apps for health purposes. These apps may improve self-management of health-related conditions. Up to 70% of pregnant women experience nausea and vomiting (NVP). Even mild NVP can significantly reduce quality of life (QoL), and it can become an economic burden for both the woman and society. NVP often occurs before the first maternal care visit; therefore, apps can potentially play an important role in empowering pregnant women to recognize, manage, and seek appropriate treatment for NVP, when required. Objective: This study investigated whether the MinSafeStart (MSS) mobile app could impact NVP-related symptoms, QoL, and decisional conflict regarding NVP treatment. Methods: This randomized controlled trial enrolled 268 pregnant women with NVP in Norway from 2019 to 2020. The intervention group had access to the MSS app, which could be used to track NVP symptoms and access tailored advice. NVP severity was rated with the Pregnancy Unique Quantification of Emesis (PUQE) score. The control group followed standard maternal care. We collected data on maternal baseline characteristics, NVP severity, QoL, and decisional conflict using 2 sets of online questionnaires. One set of questionnaires was completed at enrollment, and the other was completed after 2 weeks. We performed linear regression analyses to explore whether the use of the MSS app was associated with NVP severity, QoL, or decisional conflict. Results: Among the 268 women enrolled in the study, 192 (86.5%) completed the baseline questionnaires and were randomized to either the intervention (n=89) or control group (n=103). In the intervention group, 88 women downloaded the app, and 468 logs were recorded. In both groups, women were enrolled at a median of 8 gestational weeks. At baseline, the average PUQE scores were 4.9 and 4.7; the average QoL scores were 146 and 149; and the average DCS scores were 40 and 43 in the intervention and control groups, respectively. The app had no impact on NVP severity (aβ 0.6, 95% Cl −0.1 to 1.2), QoL (aβ −5.3, 95% Cl −12.5 to 1.9), or decisional conflict regarding NVP treatment (aβ −1.1, 95% Cl −6.2 to 4.2), compared with standard care. Conclusions: Tracking NVP symptoms with the MSS app was not associated with improvements in NVP symptoms, QoL, or decisional conflict after 2 weeks, compared with standard care. Future studies should include a process evaluation to improve our understanding of how pregnant women use the app and how to optimize its utility within maternity care. Specifically, studies should focus on how digital tools might facilitate counseling and communication between pregnant women and health care providers regarding NVP management during pregnancy.

• Favre, Guillaume; Gerbier, Eva; Maisonneuve, Emeline; Pomar, Léo; Winterfeld, Ursula & Lepigeon, Karine [Show all 14 contributors for this article] (2022). COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort. British Journal of Clinical Pharmacology. ISSN 0306-5251. doi: 10.1111/bcp.15611. Full text in Research Archive

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• Ystrøm, Eivind & Nordeng, Hedvig Marie Egeland (2025). Paracetamol i svangerskapet. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(14), p. 1164–1164. doi: 10.4045/tidsskr.25.0645. Full text in Research Archive
• Lupattelli, Angela & Nordeng, Hedvig Marie Egeland (2024). Trajectories for migraine medication in pregnancy and neurodevelopmental outcomes in offspring - a nationwide registry-based study. Full text in Research Archive
• Lupattelli, Angela; Trinh, Nhung & Nordeng, Hedvig Marie Egeland (2024). Psychiatric outcomes and their progression across different states in children and adolescents following prenatal exposure to antidepressants. Full text in Research Archive
• Trinh, Nhung; Jödicke, Annika M; Català, Martí; Mercadé-Besora, Núria; Hayati, Saeed & Lupattelli, Angela [Show all 8 contributors for this article] (2024). Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway. The Lancet Respiratory Medicine. ISSN 2213-2600. 12(5), p. e33–e34. doi: 10.1016/S2213-2600(24)00082-1. Full text in Research Archive
• Ceulemans, Michael; Sillis, Laure; Foulon, Veerle; Panchaud, Alice; Winterfeld, Ursula & Pomar, Léo [Show all 11 contributors for this article] (2022). Comment to “Pregnancy and COVID-19, focus on vaccine and pharmacological treatment”. Journal of Reproductive Immunology. ISSN 0165-0378. 152. doi: 10.1016/j.jri.2022.103639. Full text in Research Archive
• Nordeng, Hedvig Marie Egeland; Pedersen, Elisabeth; Hurley, Eimir; Zhao, Jing; Trinh, Nhung & Lupattelli, Angela (2022). EU-COVID-19 - a multinational registry-based study with focus on risk and protective factors, clinical outcomes and mental health. Full text in Research Archive
• Pedersen, Elisabeth; Lupattelli, Angela & Nordeng, Hedvig Marie Egeland (2022). Primary care diagnoses in patients developing Post COVID-19 Condition. Full text in Research Archive

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