Silvia Segovia Chacón

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: 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: Inconsistent results have been reported on the association between folic acid use in pregnancy and risk of GDM. The aim of this study was to estimate the association between folic acid use and GDM in two population-based Nordic cohorts. Material and methods: Two cohort studies were conducted using data from the national population registers in Norway (2005–2018, n = 791,709) and Sweden (2006–2016, n = 1,112,817). Logistic regression was used to estimate the associations between GDM and self-reported folic acid use and prescribed folic acid use, compared to non-users, adjusting for covariates. To quantify how potential unmeasured confounders may affect the estimates, E-values were reported. An exposure misclassification bias analysis was also performed. Results: In Norwegian and Swedish cohorts, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for maternal self-reported folic acid use were 1.10 (1.06–1.14) and 0.89 (0.85–0.93), with E-values of 1.43 (1.31) and 1.50 (1.36), respectively. For prescribed folic acid use, ORs were 1.33 (1.15–1.53) and 1.56 (1.41–1.74), with E-values of 1.99 (1.57) and 2.49 (2.17), in Norway and Sweden respectively. Conclusions: The slightly higher or lower odds for GDM in self-reported users of folic acid in Norway and Sweden respectively, are likely not of clinical relevance and recommendations for folic acid use in pregnancy should remain unchanged. The two Nordic cohorts showed different directions of the association between self-reported folic acid use and GDM, but based on bias analysis, exposure misclassification is an unlikely explanation since there may still be differences in prevalence of use and residual confounding. Prescribed folic acid is used by women with specific comorbidities and co-medications, which likely underlies the higher odds for GDM.

Introduction: For phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, the only approved indication in women is for pulmonary arterial hypertension. These drugs are increasingly being proposed and tested for treatment of female infertility and complications in pregnancy. However, the extent of use of PDE5 inhibitors in the general pregnant population over the last decades is unknown. Therefore, we conducted a descriptive cohort study using data from the population health registers in the Scandinavian countries.Material and methods: By linking the Medical Birth Registers and the Prescribed Drug Registers in Denmark (1997–2017), Norway (2004–2017), and Sweden (2006–2016), women with filled prescriptions of PDE5 inhibitors in outpatient settings in the 90 days before the date of last menstrual period and/or during pregnancies were identified. With additional linkage to the National Patient Registers, information on maternal, pregnancy, and infant characteristics, co‐morbidities, and co‐medication was collected and described.Results: Among over 3 million singleton pregnancies, only 77 were pregnancies in women who had at least one filled prescription of a PDE5 inhibitor within the 90 days before the start of pregnancy to delivery. Prescription fills most often occurred before the last menstrual period and in the first trimester, with very few occurring later in pregnancy. Sildenafil was the most used PDE5 inhibitor. Among pregnant women using PDE5 inhibitors, 44% were 35 years of age or older, eight had a cardiovascular diagnosis, and three specifically had a diagnosis of pulmonary arterial hypertension. Among the infants born to mothers using PDE5 inhibitors, nine were born preterm, six were small‐for‐gestational age, five had an Apgar score at 5 minutes below 8, 18 were admitted to the Neonatal Intensive Care Unit, and eight had respiratory and cardiovascular conditions.Conclusions: Few women used PDE5 inhibitors in outpatient settings before or during pregnancy in the Scandinavian countries in the last decades. Only a small proportion had a diagnosis for pulmonary arterial hypertension, suggesting off‐label use in the remaining users. Use was predominantly in mothers over age 35 years. The safety of fetal exposure to sildenafil and other PDE5 inhibitors in pregnancy has not been established. As maternal age continues to increase and additional uses of PDE5 inhibitors are investigated, the safety of these drugs in pregnancy should be thoroughly evaluated.