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3. Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion—12-months follow-up and safety data of the double-blind randomized PETN trial

Author

Groten, Tanja, Lehmann, Thomas, Städtler, Mariann, Komar, Matej, Winkler, Jennifer Lucia, Condic, Mateja, Strizek, Brigitte, Seeger, Sven, Jäger, Yvonne, Pecks, Ulrich, Eckmann-Scholz, Christel, Kagan, Karl Oliver, Hoopmann, Markus, von Kaisenberg, Constantin S., Hertel, Bettina, Tauscher, Anne, Schrey-Petersen, Susanne, Friebe-Hoffmann, Ulrike, Lato, Krisztian, Hübener, Christoph, Delius, Maria, Verlohren, Stefan, Sroka, Dorota, Schlembach, Dietmar, de Vries, Laura, Kraft, Katrina, Seliger, Gregor, and Schleußner, Ekkehard

Published
2024
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16. Cardiovascular health of women 10 to 20 years after placenta-related pregnancy diseases considering the possible effect of pentaerythrityl tetranitrate treatment during pregnancy on long-term maternal cardiovascular health (PAVA study).

Author

Lößner, Charlotte, Multhaup, Anna, Bäz, Laura, Lehmann, Thomas, Heimann, Yvonne, Schleußner, Ekkehard, Franz, Marcus, and Groten, Tanja

Subjects
HIGH-risk pregnancy, FETAL growth retardation, WOMEN'S health, CARDIOVASCULAR diseases, MATERNAL health, PREECLAMPSIA
Abstract

Background: Women developing preeclampsia (PE) or fetal growth restriction (FGR) during pregnancy are at higher risk for cardiovascular diseases (CVD) later in life. We aimed to analyse cardiovascular health of women 10–20 years after affected pregnancies in comparison to women after uneventful pregnancies. In addition, we assessed a potential long-term effect of the NO-donor pentaerythrityl tetranitrate (PETN). Methods: Women 10–20 years after severe PE, including women receiving PETN during pregnancy and matched controls were recruited and assessed for baseline clinical data and cardiovascular function by transthoracic echocardiography, VICORDER and USCOM. SPSS was used for statistical analysis. Results: 53 participants after PE/FGR (13 with former PETN intake) and 51 controls were recruited for follow-up at an average of 14 years after index pregnancies. Compared to controls, women after PE/FGR had a significantly higher incidence of arterial hypertension (13.7% vs. 41.5%, p<0.001), and were more likely to be hypertensive (41.2% vs. 67.30%, p = 0.008). There were no differences in cardiovascular function observed. Affected women with PETN intake during pregnancy showed lower mean values for right atrial area and ventricle in comparison to controls and also to affected women without former medication. Conclusions: In conclusion, our study results confirm that the risk of CVD is increased in women after PE/FGR compared to women after uneventful pregnancies. Contrary to our expectations, no major cardiovascular changes were observed in our cohort 10–20 years post pregnancy. The observed differences found in right heart dimensions were within reference ranges, and should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study.

Author

Rakers, Florian, Schleussner, Ekkehard, Cornelius, Amani, Kluckow, Steffen, Muth, Isabel, Hoyer, Dirk, Rupprecht, Sven, Schultze, Torsten, Schiecke, Karin, Ligges, Carolin, Schwab, Matthias, and Hoyer, Heike

Subjects
*PRENATAL exposure, *BIOLOGICAL systems, *AUTONOMIC nervous system, *NEURAL development, *HYPOTHALAMIC-pituitary-adrenal axis
Abstract

Introduction: Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long‐lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8–9 years. This follow‐up study aimed to examine whether these findings persisted into adolescence. Material and Methods: Prospective observational follow‐up study involving twenty‐one 14‐ to 15‐year‐old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty‐five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention‐deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus–pituitary–adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. Results: No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference −2.0, 95% confidence interval [CI]: −7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress‐induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency–adjusted means: 16.0 Hz vs 17.8 Hz, mean difference −1.83 Hz, 95% CI: −3.21 to −0.45, p = 0.01). Conclusions: In 14‐ to 15‐year‐old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow‐up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Effect of pentaerythritol tetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at midgestation—a randomized trial

Author

Groten, Tanja, Lehmann, Thomas, Städtler, Mariann, Komar, Matej, Winkler, Jennifer Lucia, Condic, Mateja, Strizek, Brigitte, Seeger, Sven, Jäger, Yvonne, Pecks, Ulrich, Eckmann-Scholz, Christel, Kagan, Karl Oliver, Hoopmann, Markus, von Kaisenberg, Constantin S., Brodowski, Lars, Tauscher, Anne, Schrey-Petersen, Susanne, Friebe-Hoffmann, Ulrike, Lato, Krisztian, Hübener, Christoph, Delius, Maria, Verlohren, Stefan, Sroka, Dorota, Schlembach, Dietmar, de Vries, Laura, Kraft, Katrina, Seliger, Gregor, and Schleußner, Ekkehard

Published
2023
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32. The Importance of Vaccination, Variants and Time Point of SARS-CoV-2 Infection in Pregnancy for Stillbirth and Preterm Birth Risk: An Analysis of the CRONOS Register Study.

Author

Iannaccone, Antonella, Gellhaus, Alexandra, Reisch, Beatrix, Dzietko, Mark, Schmidt, Boerge, Mavarani, Laven, Kraft, Katrina, Andresen, Kristin, Kimmig, Rainer, Pecks, Ulrich, and Schleußner, Ekkehard

Subjects
PREMATURE labor, STILLBIRTH, SARS-CoV-2, PREGNANT women, RISK assessment
Abstract

Background: The risk of preterm birth (PTB) and stillbirth increases after a SARS-CoV-2 infection during gestation. We aimed to estimate the risk depending on gestational age at infection (early <28 + 0 and late ≥28 weeks of gestation, WoG), virus variants, severity of infection, and vaccination. Methods: PTB was divided into early PTB (<32 + 0) and late PTB (32 + 0–36 + 6 WoG). The prospective register COVID-19 Related Obstetrics and Neonatal Outcome Study (CRONOS) included 8032 pregnant women with a confirmed SARS-CoV-2 infection from 3 April 2020 to 31 December 2022, in Germany and Austria. Results: Stillbirth and early preterm births rates were higher during the Alpha (1.56% and 3.13%) and Delta (1.56% and 3.44%) waves than during the Omicron wave (0.53% and 1.39%). Early SARS-CoV-2 infection increased the risk for stillbirth (aRR 5.76, 95% CI 3.07–10.83) and early PTB before 32 + 0 (aRR, 6.07, 95% CI 3.65–10.09). Hospital admission increased the risks further, especially in the case of ICU admission. Vaccination against SARS-CoV-2 significantly reduced the risk of stillbirth (aRR 0.32, 95% CI 0.16–0.83). Conclusions: This multicentric prospective study shows an increased risk of stillbirth and preterm birth after infection early in pregnancy and therefore the importance of obstetrical surveillance thereafter. Vaccination offers effective protection. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials

Author

Rodger, Marc A, Gris, Jean-Christophe, de Vries, Johanna I P, Martinelli, Ida, Rey, Évelyne, Schleussner, Ekkehard, Middeldorp, Saskia, Kaaja, Risto, Langlois, Nicole J, Ramsay, Timothy, Mallick, Ranjeeta, Bates, Shannon M, Abheiden, Carolien N H, Perna, Annalisa, Petroff, David, de Jong, Paulien, van Hoorn, Marion E, Bezemer, P Dick, and Mayhew, Alain D

Published
2016
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45. German obstetrician's self-reported attitudes and handling in threatening preterm birth at the limits of viability.

Author

Schneider, Katja, Müller, Johanna, and Schleußner, Ekkehard

Subjects
PREMATURE infants, COUNSELING, SOCIAL support, OBSTETRICIANS, PHYSICIANS' attitudes, SURVEYS, QUESTIONNAIRES, SCALE analysis (Psychology), DESCRIPTIVE statistics, RESEARCH funding, MEDICAL practice, DECISION making in clinical medicine, PRENATAL care, PARENTS, NEONATOLOGISTS
Abstract

Antenatal treatment and information influences the course of pregnancy and parental decision-making in cases of threatened prematurity on the borderline of viability. Numerous studies have shown significant interprofessional differences in assessing ethical boundary decisions; hence, this study aimed to evaluate obstetricians attitudes, practices and antenatal parental counseling regarding threatened preterm birth in Germany. An anonymous online questionnaire was administered to 543 obstetricians at tertiary perinatal centers and prenatal diagnostic centers in Germany. The survey contained questions on basic ethical issues assessed using the Likert scale and a case vignette regarding the practical procedures of an imminent extreme premature birth at 23 1/7 gestational weeks. In the case of unstoppable preterm birth, 15 % of clinicians said they would carry out a cesarean section; however, specialists from centers with a high number of very low birth weight infants would do so significantly more often. Among respondents, 29.8 % did not take any therapeutic measures without discussing the child's treatment options with their parents, 19.9 % refused to offer actionable advice to the parents, and 57 % said they would advise parents to seek intensive care treatment for the child with the option of changing treatment destination in the event of serious complications. Moreover, 84 % said they would provide information together with neonatologists. Joint counseling with neonatologists is widely accepted. The size of the perinatal center significantly influences the practical approach to threatened preterm births. Respect for parents' decision-making autonomy regarding the child's treatment options is central and influences therapy initiation. [ABSTRACT FROM AUTHOR]

Published
2023
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46. Abortion in the First Trimester. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015-094, December 2022) – Part 2 with Recommendations for Surgical Termination of Pregnancy and Follow-up Care After Termination of Pregnancy.

Author

David, Matthias, Achtenhagen, Anne, Bamberg, Christian, Bormann, Cornelia, Felderhoff-Müser, Ursula, Groth, Sylvia, Hänel, Kristina, König, Klaus, Korell, Matthias, Michl, Susanne, Redler, Silke, Schleußner, Ekkehard, Seyler, Helga, Wallwiener, Markus, and Wallwiener, Stephanie

Published
2023
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47. Abortion in the First Trimester. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015-094, December 2022) – Part 1 with Recommendations on Care Structures, Information and Advice on Decision-Making, Measures Before Abortion and Medical Abortion.

Author

David, Matthias, Achtenhagen, Anne, Bamberg, Christian, Bormann, Cornelia, Felderhoff-Müser, Ursula, Groth, Sylvia, Hänel, Kristina, König, Klaus, Korell, Matthias, Michl, Susanne, Redler, Silke, Schleußner, Ekkehard, Seyler, Helga, Wallwiener, Markus, and Wallwiener, Stephanie

Published
2023
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