Queries on medication use during pregnancy: characterisation of the Swiss Teratogen Information Service database

AIMS OF THE STUDY: Limited information on medication safety may result in concerns on how to treat pregnant and breast-feeding patients. The Swiss Teratogen Information Service (STIS) provides information to healthcare professionals about medications during pregnancy and breast feeding. Our objective was to describe the queries addressed to the STIS over the past two decades. METHODS: The STIS maintains a database of queries on pregnancy outcomes after exposure to various substances, which may be a valuable source of information. We initially analysed the general characteristics of all queries. Thereafter, we focused on exposure to medications during singleton pregnancies and associated health-related aspects. RESULTS: From 2000 to 2019, 7148 queries were entered into the database. An increasing number of queries was recorded over the study period, with an average of 357 queries entered into the database per year. Most of the enquirers were physicians; more specifically, gynaecologists/obstetricians (2389/7148; 33.4%) and psychiatrists (1007/7148; 14.1%). Two thirds (4747/7148; 66.4%) of the queries addressed medication intake during pregnancy; the next most frequent queries concerned planned medication in the context of pregnancy (928/7148; 13.0%) or medication use during breast-feeding (873/7148; 12.2%). In more than 50% (3611/7148) of cases, women were treated with more than one drug; altogether, 15193 medications (taken alone or in combination) were identified. The most frequent queries concerned medicines for the nervous system (ATC group N, n = 7042), with selective serotonin reuptake inhibitors (n = 1271) in the leading position, followed by benzodiazepine derivatives (n = 1102) and other antidepressants (n = 780). The next most frequently mentioned drug classes were anti-infectives for systemic use (J, n = 1586) and drugs for the alimentary tract and metabolism (A, n = 1205). Analysis of follow-up information on cases of medication exposure during singleton pregnancies (n = 2672) revealed an offspring malformation rate of 4.2%. The organ system most often affected was the musculoskeletal system, followed by the circulatory system; congenital malformations of the nervous system and chromosomal abnormalities were also seen. The three most frequently documented congenital diagnoses were malformations of cardiac septa, the brain and major arteries. CONCLUSIONS: Healthcare professionals often have concerns regarding the treatment of pregnant women with medication, and require professional counselling in this area. A variety of drugs are mentioned in queries addressed to the STIS, of which psycholeptics and psychoanaleptics are the most frequent. Proper guidelines on their use during pregnancy appear particularly urgent

Major malformations risk following early pregnancy exposure to metformin: a systematic review and meta-analysis.

Metformin is considered as first-line treatment for type 2 diabetes and an effective treatment for polycystic ovary syndrome (PCOS). However, evidence regarding its safety in pregnancy is limited. We conducted a systematic review and meta-analysis of major congenital malformations (MCMs) risk after first-trimester exposure to metformin in women with PCOS and pregestational diabetes mellitus (PGDM). Randomized controlled trials (RCTs) and observational cohort studies with a control group investigating risk of MCM after first-trimester pregnancy exposure to metformin were searched until December 2021. ORs and 95% CIs were calculated separately according to indications and study type using Mantel-Haenszel method; outcome data were combined using random-effects model. Eleven studies (two RCTs; nine observational cohorts) met the inclusion criteria: four included pregnant women with PCOS, four included those with PGDM and three evaluated both indications separately and were considered in both indication groups. In PCOS group, there were two RCTs (57 exposed, 52 control infants) and five observational studies (472 exposed, 1892 control infants); point estimates for MCM rates in RCTs and observational studies were OR 0.93 (95% CI 0.09 to 9.21) (I2=0%; Q test=0.31; p value=0.58) and OR 1.35 (95% CI 0.37 to 4.90) (I2=65%; Q test=9.43; p value=0.05), respectively. In PGDM group, all seven studies were observational (1122 exposed, 1851 control infants); the point estimate for MCM rates was OR 1.05 (95% CI 0.50 to 2.18) (I2=59%; Q test=16.34; p value=0.01). Metformin use in first-trimester pregnancy in women with PCOS or PGDM do not meaningfully increase the MCM risk overall. However, further studies are needed to characterize residual safety concerns

Inflammatory bowel disease (IBD)-like disease in a case of a 33-year old man with glycogenosis 1b

Background Inflammatory bowel disease (IBD)-like conditions in glycogen storage disease (GSD) type Ib have been predominantly described in children. Signs and symptoms of GSD type Ib are hypoglycemia, pancytopenia and hepatosplenomegaly. Based on few published cases, there is evidence that granulocyte-colony stimulating factor (G-CSF) in patients with glycogenosis–related pancytopenia might ameliorate the IBD-like disease through leukocyte increase. Case presentation Here we firstly describe a case of an adult 33-year-old Caucasian male patient with GSD type Ib accompanied with IBD-like disease with persistent pancytopenia despite moderate-dose G-CSF treatment. Recent vomiting and abdominal discomfort were due to a high-grade stenosis in the transverse colon. A dose increase of the G-CSF successfully normalized his leukocyte count. However, the stenosis worsened and surgical therapy was needed. Conclusion We suggest that symptomatic patients with GSD type Ib should undergo endoscopic examination in order to detect IBD-like disease and to initiate early treatment

Mental health in pregnant individuals during the COVID-19 pandemic based on a Swiss online survey.

The aim of our study was to evaluate the mental health of pregnant individuals during the early COVID-19 pandemic and the potential factors associated. A Swiss online survey was proposed to individuals who gave birth during the pandemic period from March 2020. The Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder 7 questions (GAD-7), and Impact Event Scale-Revised (IES-R) were evaluated and used to defined mental health impairment as a composite outcome. From October, 2020 to February, 2021, 736 participants responded. The anxiety GAD-7 score was moderate in 9.6% and severe in 2.0%. The EPDS was moderate in 21.5% and severe in 32.9%. The IES-R was moderate in 10.3% and severe in 3.9%. Mental health impairment was reported in 37.0%. The association between the risk of mental health impairment and foreign nationality was significant (OR = 1.48; 95%CI [1.06-2.05]) as well as fetal and pregnancy worries because of coronavirus (OR = 1.46; 95% CI [1.08-1.98]) and 1.65; 95% CI [1.22-2.24]). Adjusted ORs were significant for foreign nationality (aOR = 1.51; 95%CI [1.07-2.13]) and pregnancy worries because of coronavirus (aOR = 1.62; 95%CI [1.10-2.40]). Pregnant people and especially foreign national have a high risk of mental health impairment during the pandemic

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.

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

Antidiabetic Medication Utilisation before and during Pregnancy in Switzerland between 2012 and 2019: An Administrative Claim Database from the MAMA Cohort.

BACKGROUND The incidence of diabetes mellitus (both pregestational and gestational) is increasing worldwide, and hyperglycemia during pregnancy is associated with adverse pregnancy outcomes. Evidence on the safety and efficacy of metformin during pregnancy has accumulated resulting in an increase in its prescription in many reports. AIMS We aimed to determine the prevalence of antidiabetic drug use (insulins and blood glucose-lowering drugs) before and during pregnancy in Switzerland and the changes therein during pregnancy and over time. METHODS We conducted a descriptive study using Swiss health insurance claims (2012-2019). We established the MAMA cohort by identifying deliveries and estimating the last menstrual period. We identified claims for any antidiabetic medication (ADM), insulins, blood glucose-lowering drugs, and individual substances within each class. We defined three groups of pattern use based on timing of dispensation: (1) dispensation of at least one ADM in the prepregnancy period and in or after trimester 2 (T2) (pregestational diabetes); (2) dispensation for the first time in or after T2 (GDM); and (3) dispensation in the prepregnancy period and no dispensation in or after T2 (discontinuers). Within the pregestational diabetes group, we further defined continuers (dispensation for the same group of ADM) and switchers (different ADM group dispensed in the prepregnancy period and in or after T2). RESULTS MAMA included 104,098 deliveries with a mean maternal age at delivery of 31.7. Antidiabetic dispensations among pregnancies with pregestational and gestational diabetes increased over time. Insulin was the most dispensed medication for both diseases. Between 2017 and 2019, less than 10% of pregnancies treated for pregestational diabetes continued metformin rather than switching to insulin. Metformin was offered to less than 2% of pregnancies to treat gestational diabetes (2017-2019). CONCLUSION Despite its position in the guidelines and the attractive alternative that metformin represents to patients who may encounter barriers with insulin therapy, there was reluctance to prescribe it

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort

AIM The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy