Administration of Antenatal Corticosteroids: Optimal Timing.

The effectiveness of antenatal corticosteroids (ACS) in significantly reducing respiratory distress syndrome (RDS) depends crucially on the timing. It is successful if delivery takes place between 24 hours and seven days following administration; after this period, the side effects seem to predominate. In addition, an increased rate of mental impairment and behavioral disorders are observed in children born full-term after ACS administration. The optimal timing of ACS administration depends crucially on the given indication; to date, it has been achieved in only 25-40% of cases. ACS administration is always indicated in PPROM, in severe early pre-eclampsia, in fetal IUGR with zero or reverse flow in the umbilical artery, in placenta previa with bleeding, and in patients experiencing premature labor with a cervical length < 15 mm. The risk of women with asymptomatic cervical insufficiency giving birth within seven days is very low. In this case, ACS should not be administered even if the patient's cervical length is less than 15 mm, provided that the cervix is closed and there are no other risk factors for a premature birth. The development of further diagnostic methods with improved power to predict premature birth is urgently needed in order to optimize the timing of ACS administration in this patient population. Caution when administering ACS is also indicated in women experiencing premature labor who have a cervical length ≥ 15 mm. Further studies using amniocentesis are needed in order to identify the patient population with microbial invasion of the amniotic cavity/intra-amniotic infection (MIAC/IAI), and to define threshold values at which delivery is indicated. ACS administration is not performed as an emergency measure, usually not even before transfer to a perinatal center. Therefore, whenever possible, the indication for ACS administration should be determined by a clinician who is highly experienced in perinatology.

Statement of the Obstetrics and Prenatal Medicine Working Group (AGG - Preterm Birth Section) on "Outpatient Management for Pregnant Women with Preterm Premature Rupture of Membranes (PPROM)".

Preterm premature rupture of membranes (PPROM) is one of the leading causes of perinatal morbidity and mortality. After a PPROM, more than 50% of pregnant women are delivered within 7 days. Fetal and maternal risks are primarily due to infection and inflammation, placental abruption, umbilical cord complications and preterm birth. Standard care usually consists of an expectant approach. Management includes the administration of antenatal steroids and antibiotic therapy. Patients with PPROM require close monitoring. The management of pregnant women with PPROM (inpatient vs. outpatient) is still the subject of controversial debate. The international guidelines also do not offer a clear stance. The statement presented here discusses the current state of knowledge.

Prediction of Preterm Birth with the Uterocervical Angle in Singleton Pregnancies Treated with a Cervical Pessary.

BACKGROUND: Cervical pessaries are an established therapy option for patients at risk for spontaneous preterm birth (sPTB). The uterocervical angle (UCA) remains a promising sPTB predictor. However, its clinical significance has yet to be described in patients treated with a pessary. METHODS: This study analyzed data of patients treated with a pessary because of cervical shortening in singleton pregnancies. The patients were divided into 2 groups according to transvaginal ultrasound findings: the funneling group (n = 68) and the no-funneling group (n = 42). Moreover, we analyzed patients within these prespecified groups according to the UCA < 95° and ≥ 95°. RESULTS: Delivery occurred significantly earlier in patients treated with a pessary and with a high UCA ≥ 95°(p = 0.006). The median gestational age at delivery in patients treated with a pessary and with no funneling and a UCA < 95° vs. ≥ 95° were 39.00 and 36.14 weeks, respectively (p = 0.005). In cases with funneling and a UCA < 95° vs. ≥ 95° the mean gestational age at delivery was 38.14 and 38.07 weeks respectively (p=1,00). There was a significant negative linear correlation between UCA and the gestational age at delivery in all patients (p = 0.04), which was even profound in the group without funneling (p = 0.0002). However, we found no significant correlation between cervical length and gestational age at delivery in all patients (p = 0.42) as well as in the group without funneling (p = 0.28). CONCLUSION: In spite of pessary treatment, patients with UCA ≥ 95° presented with a higher risk of sPTB compared to patients with UCA < 95°. This suggests that the UCA seems to be a better predictor of sPTB than the cervical length in patients receiving pessary treatment.

Cervical pessary to prevent preterm birth and poor neonatal outcome: An integrity meta-analysis of randomized controlled trials focusing on adherence to the European Medical Device Regulation.

BACKGROUND: Findings from randomized trials (RCTs) on cervical pessary treatment to prevent spontaneous preterm birth are inconsistent. OBJECTIVES: Our hypothesis suggests that adhering to the European Medical Device Regulation (MDR) and following the instructions for use are essential prerequisites for successful therapy. Conversely, the non-adherence to these guidelines will probably contribute to its failure. SEARCH STRATEGY AND SELECTION CRITERIA: Based on validated criteria from integrity assessments we performed a systematic review identifying 14 RCTs evaluating the effect of cervical pessaries. DATA COLLECTION AND ANALYSIS: We analyzed the implications of 14 criteria each accounting for 0-2 points of a score reflecting the clinical evaluation plan (CEP) as proposed by the MDR to evaluate the risk-benefit ratio of medical devices. MAIN RESULTS: Seven RCTs in each singleton and twin pregnancies (5193 "cases") were included, detecting a high heterogeneity within control groups (I2 = 85% and 87%, respectively, P < 0.01). The CEP score varied from 11 to 26 points for all studies. The most common reasons for low scores and potential data compromise were poor recruitment rates, no (completed) power analysis, and no pre-registration, but mainly non-adherence to technical, biological, and clinical equivalence to the instructions for use as required by the MDR. All trials with score values greater than 20 had applied audit procedures. Within this group we found significantly reduced rates of spontaneous preterm birth at less than 34 weeks within the pessary group in singleton (odds ratio 0.28; 95% confidence interval 0.12-0.65) and twin pregnancies (odds ratio 0.30; 95% confidence interval 0.13-0.67). Similarly, there was a significant reduction in the composite poor neonatal outcome in singleton (odds ratio 0.25; 95% confidence interval 0.10-0.61) and twin pregnancies (odds ratio 0.54; 95% confidence interval 0.35-0.82) after a pessary as compared with controls. CONCLUSION: Non-audited RCTs and meta-analyses mixing studies of different clinical quality as pre-defined by a CEP and the MDR pose the risk for erroneous conclusions.

[Hyperemesis Gravidarum - an Interprofessional and Interdisciplinary Challenge - Evidence-Based Review]. / Hyperemesis gravidarum ­ eine interprofessionelle und interdisziplinäre Herausforderung.

Hyperemesis gravidarum (HG) is a multifactorial disease characterized by severe and persisting nausea and vomiting, impairment of oral intake, weight loss of at least 5%, electrolyte abnormalities, and dehydration. The prevalence of HG ranges from 0.3 to 10% worldwide. The diagnosis is made by the patient's prehistory, clinical symptoms, physical examination, and the typical laboratory abnormalities. Therapeutic cornerstones are nutrition advice, consultation of life style, psychological/psychosocial support of the mother as well as the administration of antiemetics in a stepwise approach, depending on the severity of symptoms, and finally admission to hospital in severe cases. Treatment of patients requires close interprofessional and interdisciplinary cooperation.

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

[This corrects the article DOI: 10.1055/a-2044-0203.].

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

[This corrects the article DOI: 10.1055/a-2044-0345.].

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

Aim This revised guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). It aims to improve the prediction, prevention, and management of preterm birth, based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 1 of this short version of the guideline presents statements and recommendations on the epidemiology, etiology, prediction, and primary and secondary prevention of preterm birth.

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

Aim The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

A novel aspiration technique to assess cervical remodelling in patients with or without cervical shortening: Sequence of first changes, definition of cut-off values and impact of cervical pessary, stratified for cervical length.

BACKGROUND: The therapeutic significance of the cervical pessary has been confirmed by several studies. However, the underlying mechanism by which pessaries reduce the risk of a preterm birth remains elusive. The aim of this study is to investigate the hypothesis whether the application of a cervical pessary may stabilize the ectocervical stiffness in order to achieve a cervical arrest. METHODS: This is a prospective, controlled, non-interventional, post-market, monocentric, longitudinal, cohort study in a tertiary maternity hospital to determine ectocervical stiffness and its changes measured before and after placement of a pessary in singleton pregnancies with cervical shortening in the mid trimester. In order to assess reference values for cervical stiffness, we measured also singleton pregnancies with normal cervical length in the same gestational week spectrum. The cervical stiffness measured with the Pregnolia System as the Cervical Stiffness Index (CSI, in mbar) shall be the primary endpoint, whilst patient delivery data (gestational age, mode of delivery and complications) will be the secondary endpoint. In this pilot study, up to 142 subjects will be enrolled to have a total of 120 subjects (estimated dropout rate of 15%) to complete the study; pessary cohort: 60 (up to 71 recruited), control group: 60 (up to 71 recruited). DISCUSSION: Our hypothesis is that patients with cervical shortening will present with lower CSI values and that pessary placement will be able to stabilize the CSI values through further prevention of cervical remodelling. The measurement of controls with normal cervical length shall serve as a reference.

Maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in cervical cerclage - a Germany-wide survey on the current practice after dissemination of the German guideline.

OBJECTIVES: To investigate the adherence of German perinatal specialist units and those of basic obstetric care to the national guideline we compared data from a nation-wide survey on the practice of maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in the perioperative setting of cervical cerclage, and bedrest during and after tocolysis with recommendations from the current German Guideline 015/025 "Prevention and Treatment of Preterm Birth". METHODS: A total of 632 obstetric clinics in Germany were approached and received a link to an online questionnaire. Data were descriptively analyzed by performing measures of frequency. To compare two or more groups Fisher's exact test was used. RESULTS: The response rate was 19%; 23 (19.2%) of respondents did not perform maintenance tocolysis, while 97 (80.8%) conducted maintenance tocolysis; 30 (25.0%) of obstetric units performed cervical cerclage without tocolysis and 90 (75.0%) combined cervical cerclage with tocolysis; 11 (9.2%) of respondents did not use tocolytics in patients with preterm premature rupture of membranes, while 109 (90.8%) conducted tocolysis in these patients; 69 (57.5%) of obstetric units did not recommend bed rest during tocolysis, whereas 51 (42.5%) favored bedrest. Perinatal care centers of basic obstetric care recommend bed arrest during tocolysis statistically significant more often to their patients than those of higher perinatal care levels (53.6 vs. 32.8%, p=0.0269). CONCLUSIONS: The results of our survey are in accordance to others from different countries and reveal considerable discrepancies between evidence-based guideline recommendations and daily clinical practice.

Resuscitation of Term Compromised and Asphyctic Newborns: Better with Intact Umbilical Cord?

The authors hypothesize that particularly severely compromised and asphyctic term infants in need of resuscitation may benefit from delayed umbilical cord clamping (after several minutes). Although evidence is sparse, the underlying pathophysiological mechanisms support this assumption. For this review the authors have analyzed the available research. Based on these data they conclude that it may be unfavorable to immediately clamp the cord of asphyctic newborns (e.g., after shoulder dystocia) although recommended in current guidelines to provide quick neonatological support. Compression of the umbilical cord or thorax obstructs venous flow to the fetus more than arterial flow to the placenta. The fetus is consequently cut off from a supply of oxygenated, venous blood. This may cause not only hypoxemia and consecutive hypoxia during delivery but possibly also hypovolemia. Immediate cord clamping may aggravate the situation of the already compromised newborn, particularly if the cord is cut before the lungs are ventilated. By contrast, delayed cord clamping leads to fetoplacental transfusion of oxygenated venous blood, which may buffer an existing acidosis. Furthermore, it may enhance blood volume by up to 20%, leading to higher levels of various blood components, such as red and white blood cells, thrombocytes, mesenchymal stem cells, immunoglobulins, and iron. In addition, the resulting increase in pulmonary perfusion may compensate for an existing hypoxemia or hypoxia. Early cord clamping before lung perfusion reduces the preload of the left ventricle and hinders the establishment of sufficient circulation. Animal models and clinical trials support this opinion. The authors raise the question whether it would be better to resuscitate compromised newborns with intact umbilical cords. Obstetric and neonatal teams need to work even closer together to improve neonatal outcomes.

Preterm Premature Rupture of Membranes - Inpatient Versus Outpatient Management: an Evidence-Based Review.

According to current guidelines, inpatient management until birth is considered standard in pregnant women with preterm premature rupture of membranes (PPROM). With the increasing burden on obstetric departments and the growing importance of satisfaction and right to self-determination in pregnant women, outpatient management in PPROM is a possible alternative to inpatient monitoring. The most important criterion for this approach is to ensure the safety of both the mother and the child. Due to the small number of cases (n = 116), two randomised controlled trials (RCTs) comparing inpatient and outpatient management were unable to draw any conclusions. By 2020, eight retrospective comparative studies (cohort/observational studies) yielded the following outcomes: no significant differences in the rate of maternal complications (e.g., chorioamnionitis, premature placental abruption, umbilical cord prolapse) and in neonatal morbidity, significantly prolonged latency period with higher gestational age at birth, higher birth weight of neonates, and significantly shorter length of stay of preterm infants in neonatal intensive care, shorter hospital stay of pregnant women, and lower treatment costs with outpatient management. Concerns regarding this approach are mainly related to unpredictable complications with the need for rapid obstetric interventions, which cannot be performed in time in an outpatient setting. Prerequisites for outpatient management are the compliance of the expectant mother, the adherence to strict selection criteria and the assurance of adequate monitoring at home. Future research should aim at more accurate risk assessment of obstetric complications through studies with higher case numbers and standardisation of outpatient management under evidence-based criteria.

Administration of Antenatal Corticosteroids: Current State of Knowledge.

The administration of a single course of corticosteroids before week 34 + 0 of gestation in cases with impending preterm birth is now standard procedure in obstetric care and firmly established in the guidelines of different countries. But despite the apparently convincing data, numerous aspects of this intervention have not yet been properly studied. It is still not clear which corticosteroid achieves the best results. There are very few studies on what constitutes an appropriate dose, circadian rhythms, the time frame in which corticosteroids are effective, and the balance between the risks and benefits of repeat administration. As the existing studies have rarely included patients before week 24 + 0 of gestation, we have very little information on the possible benefits of administering corticosteroids before this timepoint. If corticosteroids are administered antenatally after week 34 + 0 of gestation, the short-term benefit may be offset by the long-term adverse effect on psychomotor development. This present study summarizes the current state of knowledge regarding these issues.

Do obstetric units adhere to the evidence-based national guideline? A Germany-wide survey on the current practice of initial tocolysis.

OBJECTIVES: Current international guidelines recommend tocolytic treatment by at least 48 h to complete fetal lung maturation and to ensure in-utero transfer to a perinatal center before 34 weeks of gestation in patients with threatened preterm birth. According to the results of former surveys, significant differences between daily clinical practice patterns and evidence-based guideline recommendations regarding tocolytic treatment have been demonstrated. We compared data from a nation-wide survey on the practice of initial tocolysis with recommendations from the current German Guideline 015/025 "Prevention and Treatment of Preterm Birth". STUDY DESIGN: 632 obstetric units in Germany received a link to an online questionnaire between January 20th and March 31st 2020, which was developed according to national and international recommendations and guidelines. Collected data was descriptively analyzed by performing measures of frequency. RESULTS: The response rate was 19%; 51 (42.5%) of the respondents consider CTG tracing with ≥ 4 contractions within 20 min, 49 (40.8%) cervical length measurement of ≤ 25 mm and 13 (10.9%) subjective contractions as the most significant decision-making criteria for tocolysis; 47 (39.2%) of obstetric units initiate tocolysis earliest at 23 + 0, 34 (28.3%) at 22 + 0, 26 (21.7%) at 23 + 5 and 13 (10.8%) at 24 + 0 weeks of gestation; 104 (86.7%) stop tocolysis latest at the 34 + 0 weeks of gestation, 42 (35.0%) obstetric units administer antenatal corticosteroids at 23 + 5, 16 (13.3%) at 22 + 0, and 13 (10.8%) at 24 + 0 weeks of gestation. Calcium channel blockers are the first-line tocolytic drug used by 59 (49.1%) of the obstetric units, followed by intravenous betamimetics as bolus (n = 26, 21.7%) and atosiban (n = 20, 16.7%). Severe side-effects were observed by 105 (70%) of the respondents in association with the use of betamimetics, 14 (9.3%) with the use of nifedipine and 30 (20.0%) with nitroglycerine patches. The German guideline was considered the most important decision-making support by 78 (65%) of the obstetric units, followed by hospital specific SOPs/algorithms (n = 31, 25.8%). CONCLUSION: Our survey highlights a considerable discrepancy between evidence-based guideline recommendations and daily clinical practice.

The impact of funneling shape on the secondary prevention of spontaneous preterm birth in patients treated with either an Arabin pessary, McDonald cerclage or early total cervical occlusion (ETCO).

OBJECTIVE: Cervical funneling is associated with spontaneous preterm birth (sPTB). The aim of this analysis was to assess the relationship between funneling shape and the response to the McDonald cerclage, the Arabin pessary and the early total cervical occlusion (ETCO). METHODS: We retrospectively analyzed data of 312 randomly selected singleton pregnancies with cervical shortening <25 mm or normal cervical length and evaluated them according to the progression of funneling: control group (n = 46), cervical shortening without funneling (n = 107), V-shaped funneling (n = 68), U-shaped funneling (n = 47), and prolapse of the amniotic sac (n = 44). We evaluated sPTB rates <34, <28, <32, and <37 weeks as well as prolongation of gestation and birthweight. RESULTS: Regarding the rate of sPTB <34 weeks there was no statistical significance in either of the comparisons between control group and each of the four risk groups. Regarding prolongation of gestation we demonstrated a statistical significance for all risk groups compared to the control group (all p < .05) with the lowest prolongation rate noted in the group with amnion prolapse and the highest in the group with isolated cervical shortening without funneling. Similarly, progression of funnel shape resulted in an absolute decrease of birthweight for all risk groups compared to the control group, albeit not significant for the group with U-shaped funneling (p = .1058). CONCLUSION: Independent of the treatment, there was a significant impact of funneling shape on pregnancy duration and birthweight.

Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine - Section on Maternal Disorders.

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease specific to pregnancy. The cardinal symptom of pruritus and a concomitant elevated level of bile acids in the serum and/or alanine aminotransferase (ALT) are suggestive for the diagnosis. Overall, the maternal prognosis is good. The fetal outcome depends on the bile acid level. ICP is associated with increased risks for adverse perinatal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth. Acute fetal asphyxia and not chronic uteroplacental dysfunction leads to stillbirth. Therefore, predictive fetal monitoring is not possible. While medication with ursodeoxycholic acid (UDCA) improves pruritus, it has not been shown to affect fetal outcome. The indication for induction of labour depends on bile acid levels and gestational age. There is a high risk of recurrence in subsequent pregnancies.

[Intrahepatic cholestasis of pregnancy]. / Schwangerschaftscholestase: In Zusammenarbeit mit der AG Geburtshilfe und Pränatalmedizin in der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe ­ Sektion Maternale Erkrankungen.

Intrahepatic cholestasis of pregnancy (ICP) is the most frequent pregnancy-specific liver disease. It is characterized by pruritus and an accompanying elevation of serum bile acid concentrations and/or alanine aminotransferase (ALT), which are the key parameters in the diagnosis. Despite good maternal prognosis, elevated bile acid concentration in maternal blood is an influencing factor to advers fetal outcome. The ICP is associated with increased rates of preterm birth, neonatal unit admission and stillbirth. This is the result of acute fetal asphyxia as opposed to a chronic uteroplacental insufficiency. Reliable monitoring or predictive tools (e.g. cardiotocography (CTG) or ultrasound) that help to prevent advers events are yet to be explored. Medicinal treatment with ursodeoxycholic acid (UDCA) does not demonstrably reduce adverse perinatal outcomes but does improve pruritus and liver function test results. Bile acid concentrations and gestational age should be used as indications to determine delivery. There is a high risk of recurrence in subsequent pregnancies.