Timing of antenatal steroid administration for imminent preterm birth: results of a prospective observational study in Germany

Purpose: To evaluate the timing of antenatal steroid administration and associated medical interventions in women with imminent preterm birth. Methods: We performed a prospective observational study at a single tertiary center in Germany from September 2018 to August 2019. We included pregnant women who received antenatal steroids for imminent preterm birth and evaluated the interval from administration to birth. 120 women with antenatal steroid application were included into our analysis. Descriptive statistics were performed to analyze factors influencing the timing of antenatal steroids and to evaluate additional medical interventions which women with imminent preterm birth experience. Results: Of the 120 women included into our study, 35.8% gave birth before 34/0 weeks and 64.2% before 37/0 weeks of gestation. Only 25/120 women (20.8%) delivered within the optimal time window of 1-7 days after antenatal steroid application. 5/120 women (4.2%) only received one dose of antenatal steroids before birth and 3/120 (2.5%) gave birth within 8 to 14 days after antenatal steroids. Most women gave birth more than 14 days after steroid application (72.5%, 87/120). Women with preeclampsia (60%), PPROM (31%), and FGR (30%) had the highest rates of delivery within the optimal time window. Women of all timing groups received additional interventions and medications like antibiotics, tocolytics, or anticoagulation. Conclusion: Our observational data indicate that most pregnant women do not give birth within 7 days after the administration of antenatal steroids. The timing was best for preterm birth due to preeclampsia, PPROM, and FGR. Especially for women with symptoms of preterm labor and bleeding placenta previa, antenatal steroids should be indicated more restrictively to improve neonatal outcome and reduce untimely and unnecessary interventions. Keywords: Antenatal steroids; Corticosteroids; Prediction; Preterm birth; Respiratory distress syndrome

Study protocol designed to investigate tumour response to calcium electroporation in cancers affecting the skin:A non-randomised phase II clinical trial

INTRODUCTION: Skin malignancy is a distressing problem for many patients, and clinical management is challenging. This article describes the protocol for the Calcium Electroporation Response Study (CaEP-R) designed to investigate tumour response to calcium electroporation and is a descriptive guide to calcium electroporation treatment of malignant tumours in the skin. Calcium electroporation is a local treatment that induces supraphysiological intracellular calcium levels by intratumoural calcium administration and application of electrical pulses. The pulses create transient membrane pores allowing diffusion of non-permeant calcium ions into target cells. High calcium levels can kill cancer cells, while normal cells can restore homeostasis. Prior trials with smaller cohorts have found calcium electroporation to be safe and efficient. This trial aims to include a larger multiregional cohort of patients with different cancer diagnoses and also to investigate treatment areas using MRI as well as assess impact on quality of life. METHODS AND ANALYSIS: This non-randomised phase II multicentre study will investigate response to calcium electroporation in 30 patients with cutaneous or subcutaneous malignancy. Enrolment of 10 patients is planned at three centres: Zealand University Hospital, University Hospital of Southern Denmark and University Hospital Schleswig-Holstein. Response after 2 months was chosen as the primary endpoint based on short-term response rates observed in a prior clinical study. Secondary endpoints include response to treatment using MRI and change in quality of life assessed by questionnaires and qualitative interviews. ETHICS AND DISSEMINATION: The trial is approved by the Danish Medicines Agency and The Danish Regional Committee on Health Research Ethics. All included patients will receive active treatment (calcium electroporation). Patients can continue systemic treatment during the study, and side effects are expected to be limited. Data will be published in a peer-reviewed journal and made available to the public. TRIAL REGISTRATION NUMBERS: NCT04225767 and EudraCT no: 2019-004314-34