Pär Karlsson

Purpose: Medication use during pregnancy has increased worldwide. The aim was to investigate patterns of prescription medication use during pregnancy and postpartum in Sweden 2007–2022. Methods: We conducted a population‐based drug utilization study with linked data from the Swedish Medical Birth and Prescribed Drug Registers. From 90 days before pregnancy to 90 days after delivery, all dispensed prescriptions for each full‐level ATC code were identified. The proportion of women, by year and age, with ≥ 1 dispensed medication was calculated, as well as the number of different medications and dispensed prescriptions of structural teratogens and specific medication groups. Results: Overall, 1 065 593 (60.5%) women were dispensed ≥ 1 medication during pregnancy and 900 536 (51.1%) within 3 months postpartum. The proportion of women with ≥ 1 dispensed prescription in the postpartum period was stable but increased during pregnancy from 57.1% in 2007 to 67.5% in 2022, with the largest increase in women ≥ 40 years. The proportion using ≥ 5 different medications increased, while the proportion with a recognized or suspected structural teratogen in the first trimester remained low (< 1%). There was a notable decrease in the use of antibiotics and prescribed analgesics, and an increase in antiemetics, psychotropics, acetylsalicylic acid, anticoagulants, antihypertensives, and antidiabetics. Conclusion: Medication use during pregnancy in Sweden increased from 2007 to 2022, particularly among women ≥ 40 years, while postpartum use remained stable. Shifts in the use of specific medication groups highlight evolving maternal characteristics and clinical practice, as well as the importance of continuous surveillance and investigation of medication safety.

Background: Pain is common during pregnancy, yet there are few contemporary studies of opioid use in pregnancy. This study aimed to describe prescription analgesic opioid use during pregnancy across four regions: Oceania (New South Wales, Australia, and New Zealand), North America (Ontario, Canada, and United States), Northern Europe (Denmark, Finland, Iceland, Norway, Sweden, and United Kingdom), and East Asia (Hong Kong, South Korea, and Taiwan). Methods: A common protocol was applied to population-based data to measure analgesic opioid dispensing or prescriptions during pregnancy before birth in 2000 to 2020. The populations captured included those with public and private insurance in the United States, a sample of primary care practices in the United Kingdom, and whole-of-population cohorts in the remainder of the locations. This study examined prevalence of use, defined as at least one dispensing or prescribing and estimated trends over time. Use by sociodemographic and pregnancy characteristics is described. Results: Among a total of 20,306,228 pregnancies, 1,115,853 (55 per 1,000) had at least one analgesic opioid dispensing or prescription, ranging from 4 per 1,000 in the United Kingdom to 191 per 1,000 in the U.S. publicly insured population. The greatest relative decrease in prevalence was observed in Hong Kong (prevalence ratio, 0.2; 95% CI, 0.1 to 0.2 between 2005 and 2020), and the greatest increase was in Iceland (prevalence ratio, 4.4; 95% CI, 3.7 to 5.2 between 2004 and 2017). Codeine and tramadol were among the three most prevalent opioids in most populations. In a sensitivity analysis defining opioid use as two or more opioid -dispensing or -prescribing events, the prevalence of opioid use across populations was 17 per 1,000. Conclusions: In this large multinational study, wide global variation in the prevalence of analgesic opioid use in pregnancy was observed, yet patterns of use by sociodemographic and pregnancy characteristics were relatively consistent. Analgesic opioid use remained stable or downward trending over time in most, but not all, countries.

Purpose: To present the main findings of a post‐authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real‐world setting.Methods: This observational population‐based cohort study included data from pregnancies ending in 2006–2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified. Based on prescription fills from 90 days prior to pregnancy until delivery, infants were assigned to one of the four drug‐exposure cohorts: golimumab, other anti‐TNF biologics, other biologics, and nonbiologic systemic therapy, and the general population. Prevalence of adverse pregnancy outcomes, mortality, diagnoses of major congenital anomalies (MCA), and inpatient infections in the infants' first year of life were assessed. Odds ratios and 95% CIs were calculated for MCA and infection.Results: Among 134 infants in the golimumab cohort, none were stillborn or died in the first year of life. MCA were diagnosed in 4.5% of the infants in the golimumab cohort, versus 6.8%, 10.9%, 5.5%, and 4.6% in the other anti‐TNF biologics, other biologics, nonbiologic systemic therapy and general population cohorts, respectively. Inpatient infections were diagnosed in 11% of golimumab‐exposed infants, compared with 9%–11% of infants in the other cohorts. Unadjusted and selected adjusted comparisons showed no association between prenatal golimumab exposure and MCA or infection compared with the other exposure cohorts or general population.Conclusions: The number of infants with prenatal golimumab exposure was low, but results are reassuringly consistent with the evidence available for other anti‐TNF biologics. Continued monitoring is needed.

Background: Liver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment. Methods: Data from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group. Results: Among the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4–73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4–74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3–99.9%). Conclusion: Among patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.

Introduction: Antibiotics are often prescribed during pregnancy. Assessing the current state of prenatal antibiotic use is therefore imperative for optimizing prescribing and identifying emerging research priorities. The study aimed to describe recent trends and patterns in antibiotic use during pregnancy among women who gave birth in Sweden, including user characteristics.Material and methods: Population‐based descriptive study using linked nationwide registers. All pregnancies delivered in Sweden from 2007 to 2019 were included. Prevalence of use was defined as the percentage of pregnancies during which at least one prescription forantibiotics was filled. Temporal trends in the prevalence of antibiotic use by calendar year, trimester and weeks of gestation were assessed from time series graphs.Results: Prescriptions for systemic antibiotics were filled in 20.7% of 1 434 431 pregnancies overall, decreasing from 24.7% in 2007 to 18.0% in 2019. Phenoxymethylpenicillin (8.5%), pivmecillinam (6.5%), nitrofurantoin (4.7%), amoxicillin (1.6%) and cefadroxil (1.5%) use were the most prevalent. Their use decreased over the 13‐year period, except for pivmecillinam, which increased from 4.0% to 7.4%. Prevalence of use was highest in the second trimester (9.5%), with weekly trends peaking at 13 and 34 weeks of gestation. Compared with non‐users, antibiotic users more often belonged to the youngest and oldest age strata, carried multipleton pregnancies, had delivered before, had attained a lower education level and smoked in early pregnancy. A higher body mass index, asthma, chronic renal disease and diabetes mellitus were more prevalent among antibiotic users than among non‐users.Conclusions: Although outpatient antibiotic use during pregnancy in Sweden has been declining, one in five pregnancies was exposed to systemic antibiotics.

Background: In observational medication pregnancy safety studies, children are often followed from birth to 1 year of age. However, some major congenital malformations (MCM) may take longer to diagnose.Objectives: We aimed to investigate the proportion of children with detected MCMs at different lengths of follow‐up and compare them to the proportion detected at 1 year after birth.Methods: This population‐based register study included all singleton children liveborn in Sweden from 2006 to 2016. MCM were identified by ICD‐10 codes in the Medical Birth Register and National Patient Register, aligned to the EUROCAT classification system. Cumulative proportion of children with detected MCM at birth, 90 days, 1, 2, and 3 years was calculated and compared between children born preterm and at term.Results: In 1,138,113 liveborn children, the cumulative proportion of children with a detected MCM increased from 1.9% at birth to 3.1%, 3.9%, 4.4% and 4.7% at 90 days, 1, 2, and 3 years after birth, respectively, and varied by MCM subgroup. MCMs of the eye, ear‐face‐neck, nervous system and genitals were detected with the longest delay, with 31%–59% more detected at 3‐ versus 1‐year follow‐up. Compared to children born at term, the proportion of children with any MCM was 2.5 times higher amongst preterm children, with a higher proportion detected over the first 90 days for most MCM subgroups.Conclusions: The proportion of children with a detected MCM varied by MCM subgroup and follow‐up time. In pharmacoepidemiology studies of medication safety in pregnancy using Swedish national data, the length of child follow‐up should be chosen in accordance with the expected age at detection if a specific subgroup of MCM is under investigation, for example, eye and genital MCM require longer follow‐up for detection than abdominal wall and digestive system MCM. However, in most circumstances, 1 year of follow‐up is sufficient.

Introduction Pregabalin is an antiepileptic drug frequently prescribed to pregnant women. Risks of adverse birth and postnatal neurodevelopmental outcomes following prenatal exposure to pregabalin are uncertain. Objective To investigate the association between prenatal exposure to pregabalin and the risks of adverse birth and postnatal neurodevelopmental outcomes. Methods This study was conducted using population-based registries in Denmark, Finland, Norway, and Sweden (2005–2016). We compared pregabalin exposure against no exposure to antiepileptics and against active comparators lamotrigine and duloxetine. We obtained pooled propensity score-adjusted estimates of association using fixed-effect and Mantel–Haenszel (MH) meta-analyses. Results The total number of pregabalin-exposed births was 325/666,139 (0.05%) in Denmark, 965/643,088 (0.15%) in Finland, 307/657,451 (0.05%) in Norway, and 1275/1,152,002 (0.11%) in Sweden. The adjusted prevalence ratios (aPRs) with 95% confidence interval (CI) following pregabalin exposure versus no exposure were 1.14 (0.98–1.34) for major congenital malformations and 1.72 (1.02–2.91) for stillbirth, which attenuated to 1.25 (0.74–2.11) in MH meta-analysis. For the remaining birth outcomes, the aPRs were close to or attenuated toward unity in analyses using active comparators. Adjusted hazard ratios (95% CI) contrasting prenatal pregabalin exposure versus no exposure were 1.29 (1.03–1.63) for ADHD and attenuated when using active comparators, 0.98 (0.67–1.42) for autism spectrum disorders, and 1.00 (0.78–1.29) for intellectual disability. Conclusions Prenatal exposure to pregabalin was not associated with low birth weight, preterm birth, small for gestational age, low Apgar score, microcephaly, autism spectrum disorders, or intellectual disability. On the basis of the upper value of the 95% confidence interval, increased risks greater than 1.8 were unlikely for any major congenital malformation and ADHD. For stillbirth and most groups of specific major congenital malformations, the estimates attenuated in MH meta-analysis.