Dispensed drugs during pregnancy in outpatient care between 2015 and 2021 in Switzerland: a retrospective analysis of Swiss healthcare claims data.

AIM OF THE STUDY: We aimed to evaluate the utilisation of all prescribed drugs during pregnancy dispensed in outpatient care in Switzerland between 2015 and 2021. METHODS: We conducted a descriptive study using the Swiss Helsana claims database (2015-2021). We established a cohort of pregnancies by identifying deliveries and estimating the date of the last menstrual period. We analysed the drug burden during a 270-day pre-pregnancy period, during pregnancy (overall and by trimester), and during a 270-day postpartum period. Subsequently, we quantified 1) the median number of drug dispensations (total vs. unique drug claims); and 2) the prevalence of exposure to at least one dispensed drug and the number of dispensed drugs (0, 1, 2, 3, 4, and ≥5); and 3) the 15 most frequently dispensed drugs were identified during each period, overall and stratified by maternal age. RESULTS: Among 34,584 pregnant women (5.6% of all successful pregnancies in Switzerland), 87.5% claimed at least one drug (not including vitamins, supplements, and vaccines), and 33.3% claimed at least five drugs during pregnancy. During trimester 1 alone, 8.2% of women claimed at least five distinct drugs. The proportion of women who claimed prescribed drugs was lower pre-pregnancy (69.1%) and similar postpartum (85.6%) when compared to during pregnancy (87.5%). The most frequently claimed drugs during pregnancy were meaningfully different during pregnancy than before and after. CONCLUSIONS: This study suggests that 8 of 10 women in Switzerland are exposed to prescribed drugs during pregnancy. Most drugs dispensed during pregnancy are comparatively well investigated and are considered safe. However, the high drug burden in this vulnerable patient population underlines the importance of evidence on the benefit-risk profile of individual drugs taken during pregnancy.

The role of an advanced practice midwife in perinatal mental health: Outlining the process of role development and implementation.

INTRODUCTION: Perinatal mental health disorders (PMDs) are a global health concern. In industrialized countries, the prevalence of PMDs is estimated to be 20%, and they are associated with serious negative effects for women, their children and their families, along with high societal costs related to long-term impacts. In Switzerland, the PMD detection rate during obstetrical healthcare provision is very low (1-3%), and specialized healthcare services are limited. This study aimed to develop and implement an advanced practice midwife (APM) role at a Swiss obstetrics and gynecology hospital using the PEPPA framework to provide adequate screening and first-consultation services. METHODS: The study uses a qualitative approach and follows the research stages using the 8-step from the participatory, evidence-based, patient-focused process for advanced practice nursing role development, implementation and evaluation (PEPPA) framework to develop and implement the APM role. RESULTS: Utilizing the PEPPA framework, we were able to develop, implement, and evaluate the APM role in the field of perinatal mental health. Through appropriate screening and first-consultation services, we were able to identify affected women early and facilitate treatment. CONCLUSIONS: In addition to stakeholder engagement and interprofessional collaboration, PEPPA serves as a beneficial framework for the process of role development, implementation, and evaluation in the midwifery profession. This study aims to assist midwives with Master's degrees in establishing corresponding roles within their practice areas, thereby enhancing care delivery. Furthermore, the current APM approach is intended to be continuously evaluated to gain new insights into its effectiveness.

Neuroinflammatory reactive astrocyte formation correlates with adverse outcomes in perinatal white matter injury.

Perinatal white matter injury (WMI) is the leading cause of long-term neurological morbidity in infants born preterm. Neuroinflammation during a critical window of early brain development plays a key role in WMI disease pathogenesis. The mechanisms linking inflammation with the long-term myelination failure that characterizes WMI, however, remain unknown. Here, we investigate the role of astrocyte reactivity in WMI. In an experimental mouse model of WMI, we demonstrate that WMI disease outcomes are improved in mutant mice lacking secretion of inflammatory molecules TNF-α, IL-1α, and C1q known, in addition to other roles, to induce the formation of a neuroinflammatory reactive astrocyte substate. We show that astrocytes express molecular signatures of the neuroinflammatory reactive astrocyte substate in both our WMI mouse model and human tissue affected by WMI, and that this gene expression pattern is dampened in injured mutant mice. Our data provide evidence that a neuroinflammatory reactive astrocyte substate correlates with adverse WMI disease outcomes, thus highlighting the need for further investigation of these cells as potential causal players in WMI pathology.

Hybrid cord blood banking in a private-public-partnership: Women's perspectives.

BACKGROUND: The increasing demand for umbilical cord blood (UCB) used in stem cell transplantation led to the establishment of cord blood (CB) banks worldwide. These include public foreign donor banks and private family-directed donor banks. Recently, our department has introduced a third banking model within a private-public-partnership. This hybrid banking allows for storage of family-directed CB units, while also getting Human leukocyte antigen (HLA)-typed and included in the national stem cell donor registry. So if the need arises, the HLA-compatible CB unit can be released to an unrelated recipient as a foreign donor stem cell graft. OBJECTIVES: The aim of this study was to evaluate women's perspectives on the different CB banking options as well as retrospective satisfaction with their decisions. METHODS: We performed a prospective survey study in postpartum women, using a validated questionnaire. RESULTS: A total of 157 women were included in this survey study; 68% of them decided to have their UCB stored or donated. Among those women, 25% of them opted for hybrid storage, 72% of respondents stored UCB publicly, and 3% decided for private family-directed storage. CONCLUSIONS: Our study shows the potential of hybrid banking as an attractive UCB storage option, as an alternative to family-directed banking rather than a substitute for public donation. Hybrid storage potentially combines advantages of family-directed banking as well as unrelated CB donation expanding the number of registered CB units available for transplantation and giving every pregnant woman the possibility to store UCB.

Efficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage.

Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03-0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06-5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03-1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

All but Small: miRNAs from Wharton's Jelly-Mesenchymal Stromal Cell Small Extracellular Vesicles Rescue Premature White Matter Injury after Intranasal Administration.

White matter injury (WMI) is a common neurological issue in premature-born neonates, often causing long-term disabilities. We recently demonstrated a key beneficial role of Wharton's jelly mesenchymal stromal cell-derived small extracellular vesicles (WJ-MSC-sEVs) microRNAs (miRNAs) in WMI-related processes in vitro. Here, we studied the functions of WJ-MSC-sEV miRNAs in vivo using a preclinical rat model of premature WMI. Premature WMI was induced in rat pups through inflammation and hypoxia-ischemia. Small EVs were purified from the culture supernatant of human WJ-MSCs. The capacity of WJ-MSC-sEV-derived miRNAs to decrease microglia activation and promote oligodendrocyte maturation was evaluated by knocking down (k.d) DROSHA in WJ-MSCs, releasing sEVs containing significantly less mature miRNAs. Wharton's jelly MSC-sEVs intranasally administrated 24 h upon injury reached the brain within 1 h, remained detectable for at least 24 h, significantly reduced microglial activation, and promoted oligodendrocyte maturation. The DROSHA k.d in WJ-MSCs lowered the therapeutic capabilities of sEVs in experimental premature WMI. Our results strongly indicate the relevance of miRNAs in the therapeutic abilities of WJ-MSC-sEVs in premature WMI in vivo, opening the path to clinical application.

First Trimester Contingent Screening for Aneuploidies with Cell-Free Fetal DNA in Singleton Pregnancies - a Swiss Single Centre Experience.

Introduction: Switzerland was amongst the first countries to offer cell-free fetal DNA (cffDNA) testing covered by the health insurance to pregnant women with a risk ≥ 1:1000 for trisomies at first trimester combined screening (FTCS). The aim of this study is to evaluate the implementation of this contingent model in a single tertiary referral centre and its effect on gestational age at diagnosing trisomy 21. Materials and Methods: Between July 2015 and December 2020 all singleton pregnancies at 11-14 weeks of gestation without major fetal malformation were included and stratified according to their risk at FTCS. Statistical analysis was performed by GraphPad Version 9.1 for Windows. Results: 4424 pregnancies were included. Of 166 (3.8%) pregnancies with a NT ≥ 3.5 mm and/or a risk ≥ 1:10 at FCTS, 130 (78.3%) opted for direct invasive testing. 803 (18.2%) pregnancies had an intermediate risk, 692 (86.2%) of them opted for cffDNA first. 3455 (78.1%) pregnancies had a risk < 1:1000. 63 fetuses were diagnosed with trisomy 21, 47 (74.6%) directly by invasive procedures after FTCS, 16 (25.4%) by cffDNA first. Conclusions: Most women choose cffDNA or invasive testing as second tier according to national guidelines. Despite the delay associated with cffDNA testing after FCTS, 75% of all trisomy 21 are still diagnosed in the first trimester with this contingent screening model.

Introducing Artificial Intelligence in Interpretation of Foetal Cardiotocography: Medical Dataset Curation and Preliminary Coding-An Interdisciplinary Project.

Artificial intelligence (AI) is gaining increasing interest in the field of medicine because of its capacity to process big data and pattern recognition. Cardiotocography (CTG) is widely used for the assessment of foetal well-being and uterine contractions during pregnancy and labour. It is characterised by inter- and intraobserver variability in interpretation, which depends on the observers' experience. Artificial intelligence (AI)-assisted interpretation could improve its quality and, thus, intrapartal care. Cardiotocography (CTG) raw signals from labouring women were extracted from the database at the University Hospital of Bern between 2006 and 2019. Later, they were matched with the corresponding foetal outcomes, namely arterial umbilical cord pH and 5-min APGAR score. Excluded were deliveries where data were incomplete, as well as multiple births. Clinical data were grouped regarding foetal pH and APGAR score at 5 min after delivery. Physiological foetal pH was defined as 7.15 and above, and a 5-min APGAR score was considered physiologic when reaching ≥7. With these groups, the algorithm was trained to predict foetal hypoxia. Raw data from 19,399 CTG recordings could be exported. This was accomplished by manually searching the patient's identification numbers (PIDs) and extracting the corresponding raw data from each episode. For some patients, only one episode per pregnancy could be found, whereas for others, up to ten episodes were available. Initially, 3400 corresponding clinical outcomes were found for the 19,399 CTGs (17.52%). Due to the small size, this dataset was rejected, and a new search strategy was elaborated. After further matching and curation, 6141 (31.65%) paired data samples could be extracted (cardiotocography raw data and corresponding maternal and foetal outcomes). Of these, half will be used to train artificial intelligence (AI) algorithms, whereas the other half will be used for analysis of efficacy. Complete data could only be found for one-third of the available population. Yet, to our knowledge, this is the most exhaustive and second-largest cardiotocography database worldwide, which can be used for computer analysis and programming. A further enrichment of the database is planned.