Vertical transmission of SARS-CoV-2 - data from the German COVID-19 related obstetric and neonatal outcome study (CRONOS).

OBJECTIVES: We aimed to determine the frequency of SARS-CoV-2 positivity in newborns born to mothers with peripartum SARS-CoV-2 infection in a German cohort, to identify potential risk factors associated with neonatal SARS-CoV-2 infection, and to present short-term outcomes of newborns with vertical transmission of SARS-CoV-2. METHODS: Data on women with SARS-CoV-2 infection occurring anytime during their pregnancy was gathered prospectively within the CRONOS registry. From April 2020 to February 2023 a total of 8,540 women had been registered. The timing and the probability of mother-to-child transmission in neonates born to women with perinatal SARS-CoV-2 infection were classified using the WHO classification system. The severity of maternal infection, maternal vaccination status, type of dominant virus, and perinatal outcome parameters were analyzed as potential risk factors for neonatal SARS-CoV-2 infection. RESULTS: 6.3 % resp. 42.9 % of tested newborns and stillbirths were SARS-CoV-2 positive. 2.1 % of newborns with confirmed and possible SARS-CoV-2 infection were identified. Severe maternal COVID-19 (odds ratio 4.4, 95 % confidence interval 1.8-11.1) and maternal infection with the Delta virus (OR 3.2, 1.4-7.7) were associated with neonatal SARS-CoV-2 infection. Newborns with a confirmed or possible infection were significantly more often admitted to the NICU (65.2 % neonatal infection vs. 27.5 % non, p<0.001). CONCLUSIONS: The rate of neonatal SARS-CoV-2 positivity was higher in our cohort than previously reported, neonatal SARS-CoV-2 infections were rare. Our data emphasizes confirmative testing should be performed in newborns of SARS-CoV-2 infected mothers to identify neonatal SARS-CoV-2 infection as an underlying pathology leading to NICU admission.

[Ready to Care for Pregnant Women with Breech Presentation? - Results from an Online Survey for Midwives and Midwifery Students in Germany, Austria, and Switzerland]. / Bereit für die Betreuung von Schwangeren mit Beckenendlage? ­ Ergebnisse aus einer Onlinebefragung für Hebammen und werdende Hebammen in Deutschland, Österreich und der Schweiz.

The vaginal birth of breech presentation is an option for pregnant women supported by current German and international guidelines when favorable conditions and appropriately trained personnel are available. According to midwifery laws in the D-A-CH region, midwives should be able to provide care for a vaginal breech birth in emergencies. Therefore, imparting skills for breech delivery is enshrined in the curriculum for midwifery students. This study evaluated the knowledge and training needs of midwives and midwifery students in the German-speaking region. In May 2022, experiences, specific knowledge, and further training needs regarding vaginal breech birth were assessed through an online survey. Analysis of 467 questionnaires showed that only 30% of respondents currently attend vaginal breech births in their professional environment, but 50% would like to offer this service. 94% of respondents indicated that they would feel more confident if regular training opportunities, particularly simulations and virtual offerings, were provided for vaginal breech birth. However, currently only 10% of respondents receive regular training opportunities for vaginal breech births. The results suggest an increased provision of training opportunities for vaginal breech births to enhance midwives' safety in managing such births.

[SARS-CoV-2 Infection in Pregnancy and Incidence of Congenital Malformations - is there a Correlation? Analysis of 8032 Pregnancies from the CRONOS Registry]. / SARS-CoV-2-Infektion in der Schwangerschaft und Auftreten von angeborenen Fehlbildungen ­ Besteht ein Zusammenhang? Auswertung von 8032 Schwangerschaften aus dem CRONOS-Register.

BACKGROUND: Based on single case reports, the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS) registry, sponsored by the German Society for Perinatal Medicine (DGPM), investigated the likelihood that SARS-CoV-2 infections of the mother in (early) pregnancy cause embryopathies and/or fetopathies. MATERIAL/METHODS: The CRONOS registry enrolled a total of 8032 women with confirmed SARS-CoV-2 infection during pregnancy at more than 130 participating hospitals from April 2020 to February 2023. Both maternal and fetal data were documented and the anonymized multicenter data were analyzed. RESULTS: Of 7142 fully documented pregnancies (including postnatal data), 140 showed congenital malformations. 8.57% of the mothers had had a SARS-CoV-2-infection in the 1st trimester and 36.43% in the 2nd trimester. In 66 cases with congenital malformations (47.14%), the malformation was only detected after the diagnosis of a maternal SARS-CoV-2 infection. The overall prevalence of congenital malformations in this cohort was 1.96%, compared to a prevalence of 2.39% reported in the EUROCAT (European network of population-based registries for the epidemiological surveillance of congenital anomalies) pre-pandemic registry between 2017-2019. DISCUSSION: Our multicenter data argue against a link between maternal SARS-CoV-2 infection in early pregnancy and congenital malformation.

COVID-19, Pregnancy, and Diabetes Mellitus.

During the severe acute respiratory distress virus coronavirus type 2 (SARS-CoV-2) pandemic, many women were infected during their pregnancies. The SARS-CoV-2-induced coronavirus disease 19 (COVID-19) has an impact on maternal health and pregnancy outcomes; peripartum and perinatal morbidity and mortality are increased. Pregnancy is considered a risk factor for severe COVID-19 course. Additional risk factors during pregnancy are diabetes mellitus, gestational diabetes mellitus (GDM), and obesity. Systemic inflammation can lead to severe metabolic dysregulation with ketoacidosis. The endocrine pancreas is a target organ for SARS-CoV-2 and the fetal risk depends on inflammation of the placenta. Up to now there is no evidence that SARS-CoV-2 infection during pregnancy leads to permanent diabetes in mothers or their offspring via triggering autoimmunity or beta cell destruction. The frequently observed increased prevalence of GDM compared to the years before the pandemic is most likely due to changed lifestyle during lockdown. Furthermore, severe COVID-19 may be associated with the development of GDM due to worsening of glucose tolerance. Vaccination with a mRNA vaccine is safe and highly effective to prevent infection and to reduce hospitalization. Registries support offering evidence-based recommendations on vaccination for pregnant women. Even with the current omicron virus variant, there are increased risks for symptomatic and unvaccinated pregnant women.

Long-Term Outcome of Neonates and Infants whose Mothers Tested Positive for SARS-CoV-2 during Pregnancy - a Pilot of the Post-CRONOS Project.

OBJECTIVE: Long-term effects on infants of mothers with SARS-CoV-2 infection during pregnancy are increasingly discussed in the literature. Besides potential neurodevelopment impairments after intrauterine SARS-CoV-2 exposure, there might be differences in the postnatal pediatric care of those children, like the timing of preventive medical examinations (PME) or vaccinations. In this first national long-term follow-up study of women included in the CRONOS registry, we describe maternal impressions of their child´s development and the prevalence of regulatory disorders, and we analyze the timing of PMEs and vaccinations. METHODS: 773 women who were enrolled between April 3, 2020, and August 24, 2021, in the CRONOS registry were eligible to be contacted by the study coordinators and asked to fill out a web-based questionnaire. RESULTS: 110/773 (14%) women completed the questionnaire. Their children were between the ages of 12 and 31 months (median 20 months). All mothers were satisfied with their child´s development, milestones were achieved in a timely fashion. The reported prevalence for excessive crying, sleeping, and feeding disorders was 11%, 18-32%, and 7%, respectively. PMEs were mostly not delayed, but only 54% of infants received their first vaccination within their first 60 days of life. DISCUSSION: In summary, our exploratory findings suggest that developmental milestones in infancy are reached in time after maternal SARS-CoV-2 infection during pregnancy. However, there are effects on the implementation of PMEs and vaccinations. EINFüHRUNG: In der Literatur werden zunehmend potenzielle Langzeitfolgen für Säuglinge nach intrauteriner SARS-CoV-2-Exposition diskutiert. Neben möglichen Beeinträchtigungen der neurologischen Entwicklung können Unterschiede in der pädiatrischen postnatalen Betreuung bei diesen Kindern z. B. bei der Durchführung von Vorsorgeuntersuchungen (sog. U´s) oder Impfungen bestehen. In dieser ersten nationalen Langzeit-Follow-up-Studie aus dem CRONOS-Register beschreiben wir mütterliche Eindrücke zur Entwicklung ihres Kindes, sowie die Prävalenz von Regulationsstörungen. Wir analysieren den Zeitpunkt von U´s und Impfungen. METHODEN: 773 Frauen, die zwischen dem 03.04.2020 und dem 24.08.2021 in CRONOS aufgenommen wurden, wurden von den Studienkoordinatoren kontaktiert und gebeten, einen webbasierten Fragebogen auszufüllen. ERGEBNISSE: 110/773 (14%) Frauen füllten den Fragebogen aus, ihre Kinder waren zwischen 12 und 31 Monate alt (Median 20 Monate). Alle Mütter waren mit der Entwicklung ihres Kindes zufrieden, Meilensteine der Entwicklung wurden zeitgerecht erreicht. Die berichtete Prävalenz für exzessives Schreien, Schlaf- und Fütterstörungen betrug 11%, 18-32% bzw. 7%. U´s wurden meist zeitgerecht durchgeführt, aber nur 54% der Säuglinge erhielten ihre erste Impfung innerhalb der ersten 60 Lebenstage. DISKUSSION: Zusammenfassend deuten unsere explorativen Ergebnisse darauf hin, dass Entwicklungsmeilensteine im Säuglingsalter nach mütterlicher SARS-CoV-2-Infektion in der Schwangerschaft rechtzeitig erreicht werden. Es zeigen sich jedoch Auswirkungen auf die Durchführung von Vorsorgen und Impfungen.

Post-COVID in women after SARS-CoV-2 infection during pregnancy - a pilot study with follow-up data from the COVID-19-related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Pregnant women are at an increased risk of severe COVID-19 and adverse pregnancy outcomes; data on maternal long-term outcome is scarce. We analyzed long-term follow-ups on women who experienced a SARS-CoV-2 infection during pregnancy to evaluate post-COVID symptoms, particularly fatigue, and their association with quality of life (QoL). METHODS: 773 women who enrolled in the CRONOS registry between April 2020 and August 2021 were contacted for follow-up from December 2022 to April 2023. Data was gathered through a web-based questionnaire. Subsequently, study coordinators matched the follow-up data with the existing CRONOS data. RESULTS: 110/773 (14%) women provided data. 20.9% experienced only acute symptoms during their SARS-CoV-2 infection in pregnancy, while 2.7% women experienced symptoms lasting longer than 4 weeks (long COVID). Symptoms lasting longer than 12 weeks (post-COVID) were reported by 63.6% women and occurred more often after severe COVID-19. Fatigue was the most frequently reported symptom (88%), with 55% of women still experiencing it more than one year after initial infection. 76% of women rated their QoL as "good" or "very good". Women experiencing post-COVID reported a significantly lower QoL. CONCLUSION: This is the first German long-term data on women after SARS-CoV-2 infection during pregnancy, showing a high rate of post-COVID, a persistence of fatigue, and the impact on QoL. Continuous monitoring of pregnant women with COVID-19 is needed to develop comprehensive management strategies.

Prevalence and Obstetric Management Changes During the COVID-19 Pandemic in Peripartum SARS-CoV-2-Positive Women - an Analysis of the CRONOS Registry Data.

The analysis of CRONOS data for this article presents the infection prevalence among parturients and subsequent changes in obstetric management over time in Germany. 2,184 women with peripartum SARS-CoV-2 infection (<14d before birth) were included. Monthly period prevalence was calculated using the number of affected women on the CRONOS registry relative to total monthly births in each hospital from March 2020 to May 2022 and compared to RKI data. Trends related to changes in obstetric management were calculated based on severity of illness. By June 2021, the obstetric population shows a discretely higher infection prevalence compared to the general population, falling below the RKI reported prevalence by October 2021. The overall rate of iatrogenic deliveries remains unchanged over time (p-value for trend=0.779). During wave 1 to 4, deliveries due to SARS-CoV-2 infection rose among moderately to severely ill women (p-value for trend 0.0000) and was increased compared to moderately ill women (p=0.001). We showed that comprehensive screening provides timely information on infection prevalence. Recruitment fatigue caused by higher clinician workload due to increased admissions and more cases with severe illness probably caused reduced prevalence reporting. Changes in obstetric management were related to COVID-19 symptom severity. A comprehensive national perinatal registry is needed to examine other areas of perinatal care in Germany.

Breastfeeding Rates During the COVID-19 Pandemic in Germany: Data from the CRONOS Registry.

SARS-CoV-2 infection and COVID-19 disease are thought to have an impact on breastfeeding rate - besides other known peripartal issues. Data of the national CRONOS registry regarding breastfeeding behavior in 6,746 women was analyzed regarding the time window between maternal SARS-CoV-2 infection and time of delivery. In addition, other influencing factors like the predominant viral variant, maternal disease severity, and gestational age at delivery were taken into account. Our data suggest that within the variables analyzed, in the case of acute maternal infection (<14 days before birth), breastfeeding behavior improved with increasing gestational age at birth (p<0.0001), with less severe maternal illness (p<0.0001) and as the pandemic progressed with less virulent viral variants (p=0.01). When adjusting for COVID-19-associated and non-associated factors, rooming-in remains the most important factor positively influencing breastfeeding behavior. With regards to the benefits for mother and infants from breastfeeding, a separation of mother and child even in case of infectious settings should be avoided.

Evolution of Fetal Growth in Symptomatic Sars-Cov-2 Pregnancies.

INTRODUCTION: SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth. MATERIALS & METHODS: CRONOS is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 symptoms, pregnancy- and delivery-specific information were recorded. The data evaluated in this study range from March 2020 until August 2021. Women with SARS-CoV-2 were divided into three groups according to the time of infection/symptoms to delivery: Group I<2 weeks, Group II 2-4 weeks, and Group III>4 weeks. FGR was defined as estimated and/or birth weight<10% ile, appropriate for gestational age (AGA) was within 10 and 90%ile, and large for gestational age (LGA) was defined as fetal or neonatal weight>90%ile. RESULTS: Data for a total of 2,650 SARS-CoV-2-positive pregnant women were available. The analysis was restricted to symptomatic cases that delivered after 24+0 weeks of gestation. Excluding those cases with missing values for estimated fetal weight at time of infection and/or birth weight centile, 900 datasets remained for analyses. Group I consisted of 551 women, Group II of 112 women, and Group III of 237 women. The percentage of changes from AGA to FGR did not differ between groups. However, there was a significantly higher rate of large for gestational age (LGA) newborns at the time of birth compared to the time of SARS-CoV-2 infection in Group III (p=0.0024), respectively. CONCLUSION: FGR rates did not differ between symptomatic COVID infections occurring within 2 weeks and>4 weeks before birth. On the contrary, it presented a significant increase in LGA pregnancies in Group III. However, in this study population, an increase in the percentage of LGA may be attributed to pandemic measures and a reduction in daily activity.

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

BACKGROUND: Fetal growth restriction is strongly associated with impaired placentation and abnormal uteroplacental blood flow. Nitric oxide donors such as pentaerythritol tetranitrate are strong vasodilators and protect the endothelium. Recently, we demonstrated in a randomized controlled pilot study a 38% relative risk reduction for the development of fetal growth restriction or perinatal death following administration of pentaerythritol tetranitrate to pregnant women at risk, identified by impaired uterine perfusion at midgestation. Results of this monocenter study prompted the hypothesis that pentaerythritol tetranitrate might have an effect in pregnancies with compromised placental function as a secondary prophylaxis. OBJECTIVE: This study aimed to test the hypothesis that the nitric oxide donor pentaerythritol tetranitrate reduces fetal growth restriction and perinatal death in pregnant women with impaired placental perfusion at midgestation in a multicenter trial. STUDY DESIGN: In this multicenter, randomized, double-blind, placebo-controlled trial, 2 parallel groups of pregnant women presenting with a mean uterine artery pulsatility index >95th percentile at 19+0 to 22+6 weeks of gestation were randomized to 50-mg Pentalong or placebo twice daily. Participants were assigned to high- or low-risk groups according to their medical history before randomization was performed block-wise with a fixed block length stratified by center and risk group. The primary efficacy endpoint was the composite outcome of perinatal death or development of fetal growth restriction. Secondary endpoints were neonatal and maternal outcome parameters. RESULTS: Between August 2017 and March 2020, 317 participants were included in the study and 307 were analyzed. The cumulative incidence of the primary outcome was 41.1% in the pentaerythritol tetranitrate group and 45.5% in the placebo group (unadjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; adjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; P=.43). Secondary outcomes such as preterm birth (unadjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; adjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; P=.01) and pregnancy-induced hypertension (unadjusted relative risk, 0.65; 95% confidence interval, 0.46-0.93; adjusted relative risk, 0.65; 95% confidence interval, 0.46-0.92; P=0.01) were reduced. CONCLUSION: Our study failed to show an impact of pentaerythritol tetranitrate on the development of fetal growth restriction and perinatal death in pregnant women with impaired uterine perfusion at midgestation. Pentaerythritol tetranitrate significantly reduced secondary outcome parameters such as the incidence of preterm birth and pregnancy-induced hypertension in these pregnancies.

Predicting adverse outcomes in pregnant patients positive for SARS-CoV-2: a machine learning approach- a retrospective cohort study.

BACKGROUND: Pregnant people are particularly vulnerable to SARS-CoV-2 infection and to ensuing severe illness. Predicting adverse maternal and perinatal outcomes could aid clinicians in deciding on hospital admission and early initiation of treatment in affected individuals, streamlining the triaging processes. METHODS: An international repository of 1501 SARS-CoV-2-positive cases in pregnancy was created, consisting of demographic variables, patient comorbidities, laboratory markers, respiratory parameters, and COVID-19-related symptoms. Data were filtered, preprocessed, and feature selection methods were used to obtain the optimal feature subset for training a variety of machine learning models to predict maternal or fetal/neonatal death or critical illness. RESULTS: The Random Forest model demonstrated the best performance among the trained models, correctly identifying 83.3% of the high-risk patients and 92.5% of the low-risk patients, with an overall accuracy of 89.0%, an AUC of 0.90 (95% Confidence Interval 0.83 to 0.95), and a recall, precision, and F1 score of 0.85, 0.94, and 0.89, respectively. This was achieved using a feature subset of 25 features containing patient characteristics, symptoms, clinical signs, and laboratory markers. These included maternal BMI, gravidity, parity, existence of pre-existing conditions, nicotine exposure, anti-hypertensive medication administration, fetal malformations, antenatal corticosteroid administration, presence of dyspnea, sore throat, fever, fatigue, duration of symptom phase, existence of COVID-19-related pneumonia, need for maternal oxygen administration, disease-related inpatient treatment, and lab markers including sFLT-1/PlGF ratio, platelet count, and LDH. CONCLUSIONS: We present the first COVID-19 prognostication pipeline specifically for pregnant patients while utilizing a large SARS-CoV-2 in pregnancy data repository. Our model accurately identifies those at risk of severe illness or clinical deterioration, presenting a promising tool for advancing personalized medicine in pregnant patients with COVID-19.

Intrahepatic cholestasis of pregnancy: an evaluation of obstetric management in German maternity units.

PURPOSE: Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse fetal and neonatal outcome. Evidence for improvement by obstetric management is sparse. Common international guidelines recommend induction of labor before term, however, they differ in recommendations of monitoring the disease and time point of active management. So far, an official guideline for treatment and management of ICP in Germany does not exist. This study aims to compile common practice and policy in obstetric management of ICP in German maternity units. The objective is to gather obstetricians' opinion on management of ICP, and to estimate the need for standardization of current practice in Germany on the background of existing evidence. METHODS: A questionnaire focusing on indications for interventions was developed including fourteen multiple-choice questions comprising the areas of diagnostic criteria, laboratory testing, fetal monitoring, treatment, and delivery timing. The survey was sent to 699 maternity clinics and was distributed to participants of the annual congress hosted by the German society of perinatal medicine (DGPM). Collected data were summarized and evaluated in relation to available evidence and existing guidelines. Descriptive statistics and Fisher's exact test were used. RESULTS: 334 completed questionnaires returned corresponding to a response rate of 48.1%. Coinciding with existing international guidelines, 48.8% of the participants acknowledge bile acid concentrations above 10 µmol/L to be indicative of ICP. 85.0% of obstetricians recommend antenatal testing with cardiotocography, exceeding common standards of maternity policy guidelines; 50.3% execute active management in ICP-affected pregnancies as they generally recommend a delivery between 37 + 0 and 38 + 6 weeks of gestation. Although recent studies evinced a risk of stillbirth in ICP-affected pregnancies not until a bile acid concentration of > 100 µmol/L, 22.2% of the respondents recommend delivery before 37 + 0 weeks of gestation due to raised bile acids of 40-99 µmol/L. CONCLUSIONS: Opinions on the management of ICP in German maternity units differ widely and partly deviate by large from international standards. Reasons for this may be the lack of a national guideline and the low awareness due to the rarity of the disease on the one hand and the very slow dynamics in evidence generation and thus the uncertainty about the actual risks and optimal management on the other. The present data highlight the need for further research and clinical guidelines to standardize and optimize treatment based on the best available evidence.

[Acute Fatty Liver of Pregnancy - Case Series]. / Akute Schwangerschaftsfettleber ­ Fallserie einer seltenen Schwangerschaftskomplikation.

With a prevalence of 0,01-0,03%, acute fatty liver in pregnancy (AFLP) is a rare and dangerous complication of pregnancy and is difficult to distinguish from other, sometimes more common, pregnancy diseases such as HELLP syndrome, aHUS and TTP because of its mostly non-specific symptoms. Due to its rarity, AFLP is often not obvious to the obstetrician as a possible differential diagnosis. Yet early diagnosis and the fastest possible delivery is the only causal therapy and is important for the mortality rate. In the present manuscript, the pathophysiology, diagnosis and therapy of acute fatty liver in pregnancy are highlighted for the clinical routine based on case descriptions from three university hospitals, and reference is made to possible findings that are helpful in establishing the diagnosis. The angiogenic preeclampsia marker sFlt-1 plays a role and provides new opportunities to consider pathophysiological approaches.

[SARS-CoV-2/COVID-19 and Hypertensive Pregnancy Disorders: Evaluation of the CRONOS National Registry]. / Hypertensive Schwangerschaftserkrankungen und SARS-CoV-2/COVID-19: Auswertung des nationalen CRONOS-Registers.

SARS-CoV-2 infection and COVID-19 disease are associated with an increased risk of hypertensive pregnancy disease in international registry studies. Preexisting hypertensive disorders are recognized as a risk factor of severe COVID-19 progression in pregnancy. The respective damage to the endothelium is discussed as a pathophysiological commonality of both diseases.Data of the national CRONOS registry (data status 05/2021; 1104 pregnant women with SARS-CoV-2 infection) were analyzed regarding the association of hypertensive pregnancy disease and maternal, pregnancy, neonatal, and COVID-19 disease outcomes. In the presence of hypertensive pregnancy disease, a severe combined outcome of pregnancy (17.3 vs. 4.3%, p=0.001), mother (25.0 vs. 9.4%, p=0.001), and newborn (28.8 vs. 9.1%, p<0.0005) occurred significantly more frequent. In contrast, the outcome of COVID-19 disease did not differ (3.8 vs. 7.5%, p=0.424). The co-occurrence of SARS-CoV-2 infection and hypertensive pregnancy disease should be acknowledged as risk factor during management decisions.

[Postpartum Hemorrhage]. / Postpartale Hämorrhagie.

Postpartum hemorrhage (PPH) affects about 4% of all deliveries in high-income countries and continues to rise, a trend attributable to the increase in caesarean section rates and maternal morbidity. Preventive measures such as the precautionary administration of uterotonics effectively reduce the risk of severe bleeding irrespective of birth mode. As a time-critical condition and a significant contributor to adverse maternal outcomes, PPH needs to be diagnosed early by measuring, not estimating, blood losses. Institutional treatment algorithms should be available to guide stage-based interdisciplinary management without delay. The main therapy goals are to identify the etiology and stop the bleeding by using uterotonics and mechanical and surgical interventions, to restore hemodynamic stability by volume and transfusion therapy and to optimize hemostasis by laboratory- and viscoelastic assay-guided factor replacement. This review highlights current recommendations for prevention, diagnosis and treatment of PPH.

[Pregnant in the Intensive Care Unit]. / Schwanger auf der Intensivstation.

Although admission to an intensive care unit during pregnancy is rare, pregnant women may become critically ill due to either obstetric or non-obstetric illness. Whilst critical illness due to obstetric reasons during the peripartum period (e.g. peripartum haemorrhage, HELLP-syndrome) is more common, it is also important to know how to care for critically ill pregnant women with non-obstetric illness (e.g. infection, cardiovascular diseases, neurological diseases, trauma). Physiological changes during pregnancy may affect critical care treatment, variation in standard and target values for blood pressure management or artificial ventilation. Pregnancy specific reference values in interpretation of blood chemistry are important issues to consider. The use of different drugs is inevitable in critical care, knowing which drugs are safe to use during the different stages of pregnancy is essential. Caring for mother and unborn child in the ICU is a challenge, open communication, ethical considerations and interdisciplinary as well as multiprofessional collaborations should be key points when caring for critically ill pregnant patients.

Maternal and neonatal outcomes of pregnancies with COVID-19 after medically assisted reproduction: results from the prospective COVID-19-Related Obstetrical and Neonatal Outcome Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 infections in pregnancy have been associated with maternal morbidity, admission to intensive care, and adverse perinatal outcomes such as preterm birth, stillbirth, and hypertensive disorders of pregnancy. It is unclear whether medically assisted reproduction additionally affects maternal and neonatal outcomes in women with COVID-19. OBJECTIVE: To evaluate the effect of medically assisted reproduction on maternal and neonatal outcomes in women with COVID-19 in pregnancy. STUDY DESIGN: A total of 1485 women with COVID-19 registered in the COVID-19 Related Obstetric and Neonatal Outcome Study (a multicentric, prospective, observational cohort study) were included. The maternal and neonatal outcomes in 65 pregnancies achieved with medically assisted reproduction and in 1420 spontaneously conceived pregnancies were compared. We used univariate und multivariate (multinomial) logistic regressions to estimate the (un)adjusted odds ratios and 95% confidence intervals for adverse outcomes. RESULTS: The incidence of COVID-19-associated adverse outcomes (eg, pneumonia, admission to intensive care, and death) was not different in women after conceptions with COVID-19 than in women after medically assisted reproduction pregnancies. Yet, the risk of obstetrical and neonatal complications was higher in pregnancies achieved through medically assisted reproduction. However, medically assisted reproduction was not the primary risk factor for adverse maternal and neonatal outcomes including pregnancy-related hypertensive disorders, gestational diabetes mellitus, cervical insufficiency, peripartum hemorrhage, cesarean delivery, preterm birth, or admission to neonatal intensive care. Maternal age, multiple pregnancies, nulliparity, body mass index >30 (before pregnancy) and multiple gestation contributed differently to the increased risks of adverse pregnancy outcomes in women with COVID-19 independent of medically assisted reproduction. CONCLUSION: Although women with COVID-19 who conceived through fertility treatment experienced a higher incidence of adverse obstetrical and neonatal complications than women with spontaneous conceptions, medically assisted reproduction was not the primary risk factor.

Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. OBJECTIVE: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. STUDY DESIGN: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. RESULTS: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight. CONCLUSION: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.

Chronic Deciduitis With Plasma Cells: A Quantitative and Clinicopathological Analysis Concerning Different Trimesters.

Background: Chronic deciduitis is a chronic inflammatory placental disease. It is associated with severe perinatal complications, especially recurrent miscarriage, preterm birth, preterm labor, and preterm prelabor rupture of membranes.Methods: This study presents a detailed quantification of plasma cells and lymphocytes, and regards clinicopathological associations concerning different trimesters in 99 cases displaying chronic deciduitis with plasma cells (CD), 23 cases from the second trimester and 76 cases from the third trimester, respectively. The control group without CD consisted of matched placentas concerning the gestational weeks.Results: In every instance lymphocytes were more numerous than plasma cells. The mean value/highest score in ten high power fields were 50/321 for plasma cells, and 460/995 for lymphocytes, respectively. In the second trimester the scores for plasma cells were significantly higher than in the third trimester. In the third trimester preterm labor occurred significantly more often in cases with chronic deciduitis related to the control group (P < .05).Conclusion: In chronic deciduitis the plasma cell count is usually higher in the second compared to the third trimester. A brisk infiltration of the decidua with plasma cells could probably point to a more severe clinical manifestation and a higher risk for preterm labor and preterm birth.

Hypertensive disease, preterm birth, fetal growth restriction and chronic inflammatory disorders of the placenta: experiences in a single institution with a standardized protocol of investigation.

PURPOSE: Chronic inflammatory disorders of the placenta, in particular villitis of unknown etiology (VUE), chronic deciduitis (CD), chronic chorioamnionitis (CC), chronic histiocytic intervillositis (CHI), and eosinophilic/T-cell chorionic vasculitis (ETCV) can exclusively be diagnosed histologically. Using a standardized procedure for submission and pathological-anatomical examination of placentas in a single perinatal care center, we analyzed the association of chronic placental lesions to perinatal complications. METHODS: We reviewed all singleton placentas and miscarriages that were examined histologically over a period of ten years after having implemented a standardized protocol for placental submission in our hospital. Cases with chronic inflammatory lesions were identified, and clinical data were analyzed and compared with a focus on preterm birth, hypertensive disorders, and fetal growth restriction and/or fetal demise. RESULTS: In 174 placentas, at least one of the chronic inflammatory entities was diagnosed. CD was the most frequent disorder (n = 95), and had strong associations with preterm birth (47.3% of all cases with CD) and intrauterine fetal demise. VUE (n = 74) was exclusively diagnosed in the third trimester. This disorder was associated with a birth weight below the 10th percentile (45% of the cases) and hypertensive disease in pregnancy. Miscarriage and intrauterine fetal demise were associated with CHI (in 66.7% of cases, n = 18). CONCLUSIONS: Chronic inflammatory disorders are frequently observed and contribute to major obstetric and perinatal complications. Further studies are needed to get a better picture of the connection between adverse obstetric outcomes and chronic inflammation to aid in the better counseling of patients.