Minerals and the Menstrual Cycle: Impacts on Ovulation and Endometrial Health.

The role of minerals in female fertility, particularly in relation to the menstrual cycle, presents a complex area of study that underscores the interplay between nutrition and reproductive health. This narrative review aims to elucidate the impacts of minerals on key aspects of the reproductive system: hormonal regulation, ovarian function and ovulation, endometrial health, and oxidative stress. Despite the attention given to specific micronutrients in relation to reproductive disorders, there is a noticeable absence of a comprehensive review focusing on the impact of minerals throughout the menstrual cycle on female fertility. This narrative review aims to address this gap by examining the influence of minerals on reproductive health. Each mineral's contribution is explored in detail to provide a clearer picture of its importance in supporting female fertility. This comprehensive analysis not only enhances our knowledge of reproductive health but also offers clinicians valuable insights into potential therapeutic strategies and the recommended intake of minerals to promote female reproductive well-being, considering the menstrual cycle. This review stands as the first to offer such a detailed examination of minerals in the context of the menstrual cycle, aiming to elevate the understanding of their critical role in female fertility and reproductive health.

Obstetric and Neonatal Outcomes Following Hospital Transfers of Home Births and Births in Midwife-led Units in Austria.

Introduction: Home births and births in midwife-led units and the associated potential risks are still being debated. An analysis of the quality of results of planned home births and births in midwife-led units which require intrapartum transfer of the mother to hospital provides important information on the quality of processes during births which occur outside hospital settings. The aim of this study was to analyze neonatal and maternal outcomes after the initial plan to deliver at home or in a midwife-led unit had to be abandoned and the mother transferred to hospital. Material and Methods: The method used was an analysis of data obtained from the Austrian Birth Registry. The dataset consisted of singleton term pregnancies delivered in the period from 1 January 2017 to 31 December 2021 (n = 286056). For the analysis, two groups were created for comparison (planned hospital births and hospital births recorded in the Registry as births originally planned as home births or births in midwife-led units but which required a transfer to hospital) and assessed with regard to previously defined variables. Data were analyzed using frequency description, bivariate analysis and regression models. Results: In Austria, an average of 19% of planned home births have to be discontinued and the mother transferred to hospital. Home births and births in midwife-led units which require transfer of the mother to hospital are associated with higher intervention rates intrapartum, high rates of vacuum delivery, and higher emergency c-section rates compared to planned hospital births. Multifactorial regression analysis showed significantly higher risks of poorer scores for all neonatal outcome parameters (Apgar score, pH value, transfer rate). Conclusion: If a birth which was planned as a home delivery or as a delivery in a midwife-led unit fails to progress because of (possible) anomalies, the midwife must respond and transfer the mother to hospital. This leads to a higher percentage of clinical interventions occurring in hospital. From the perspective of clinical obstetrics, it is understandable, based on the existing data, that giving birth outside a clinical setting cannot be recommended.

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.

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.

Synthetic Osmotic Dilators for Pre-Induction Cervical Ripening - an Evidence-Based Review.

Mechanical methods have gained growing interest for pre-induction cervical ripening in women with an unripe cervix, since they have a better safety profile compared to prostaglandins. Balloon catheters have been the gold standard method for decades, while there was a lack of data on synthetic osmotic cervical dilators. Not until 2015, when Dilapan-S was approved by the Food and Drug Administration (FDA) for induction of labor, numerous studies have been published on the use of Dilapan-S in this field. The rate of vaginal deliveries associated with the use of Dilapan-S ranges from 61.6 to 81.7%, and no serious complications needing further interventions have been reported to this date. Dilapan-S was shown to be as effective as the Foley balloon catheter as well as the 10 mg PGE 2 vaginal insert and orally applied misoprostol (25 µg every 2 hours) in achieving vaginal delivery, but patient's satisfaction during the cervical ripening process was significantly higher compared to the other methods and the rate of uterine hyperstimulation was significantly lower compared to prostaglandins (PGs). Minor complications (e.g. vaginal bleeding) associated with the use of Dilapan-S were < 2%, and maternal infectious morbidity was not higher compared to Foley balloon and vaginal PGE 2 or misoprostol. Due to these beneficial properties Dilapan-S might be an ideal option for outpatient cervical ripening, as shown in a recent randomized clinical trial comparing inpatient to outpatient cervical ripening. Furthermore, according to the manufacturers' product information, Dilapan-S is the only cervical ripening method that is not contraindicated for induction of labor in women with a previous cesarean section. Upcoming guidelines should consider synthetic osmotic cervical dilators as an effective and safe method for cervical ripening/induction of labor acknowledging that more evidence-based data are mandatory, particularly in patients with a previous cesarean section.

Breastfeeding in primiparous women - expectations and reality: a prospective questionnaire survey.

BACKGROUND: Breastfeeding provides the optimal nutrition for infants and offers numerous benefits for both mother and child. The World Health Organisation recommends exclusive breastfeeding during the first 6 months of life and the introduction of complementary feeding between the fifth and seventh months of life. There is a discrepancy between breastfeeding recommendations and the actual duration of breastfeeding. The aim of this study was to analyse breastfeeding behaviour in primiparous women in order to be able to provide support for mothers. METHODS: In this prospective, questionnaire-based study conducted between 2020 and 2022, primiparous women were asked to complete three questionnaires at three defined survey time points (routine prepartum presentation, postpartum hospitalization, completed sixth month of life). RESULTS: A total of 140 women were included and returned all three questionnaires. Fifty-eight percent performed breastfeeding exclusively at least until their baby had reached the age of 6 months, whereas 20% already stopped within the first 6 months. The main reasons given for early cessation were insufficient milk supply and inadequate infant weight gain. A comprehensive level of prepartum knowledge had a significant positive effect on participants' sense of confidence with breastfeeding. Sociodemographic factors such as age and educational level were also associated with breastfeeding behaviour, but significant corresponding differences in the duration of breastfeeding were not observed. Women with postpartum midwifery care breastfed significantly longer (p < 0.05). CONCLUSIONS: Breastfeeding behaviour and duration are influenced by multiple factors. Although certain sociodemographic factors are unalterable, comprehensive prepartum knowledge transfer and postpartum midwifery care have a positive impact on breastfeeding behaviour. TRIAL REGISTRATION: The study was retrospectively registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) on 6 December 2022 (DRKS00030763).

Effects of age on the diagnostic value of the soluble fms-like tyrosine kinase-1/ placental growth factor ratio in preeclampsia: a retrospective cohort study.

OBJECTIVE: Measurement of the ratio between soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) supports the diagnosis of preeclampsia. sFlt-1/PlGF ratios of at least 85 and at least 110 have previously been suggested for diagnosis of early-onset and late-onset preeclampsia, respectively. However, angiogenic and antiangiogenic factors change throughout the process of aging, potentially influencing preeclampsia diagnosis. In this study, we therefore evaluated in detail the effect of maternal age on sFlt-1/PlGF ratios. METHODS: A total of 2775 pregnant female patients were included in this retrospective cohort study, spread across three maternal age groups: 18-25 years, 26-35 years, and more than 35 years at delivery. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate sFlt-1/PlGF ratio cutoffs for use in preeclampsia diagnosis. RESULTS: Controls (2462 pregnant women) showed a significant difference in sFlt-1/PlGF ratios between the youngest and oldest age groups, which resulted in differences in the best-performing sFlt-1/PlGF ratio cutoffs: optimized cutoffs were 143.4 (52.9%, 98.2%), 8.6 (84.4%, 75.3%), and 22.9 (78.6%, 82.3%) in early-onset preeclampsia, and 46.4 (67.5%, 81.5%), 40.8 (77.3%, 73%), and 44.1 (65.1%, 74.5%) in late-onset preeclampsia in age groups, 1, 2, and 3, respectively. CONCLUSION: sFlt-1/PlGF ratios change with maternal age, which has important clinical implications for their use in the diagnosis of preeclampsia: Better differentiated sFlt-1/PlGF cutoffs should be used that take maternal and gestational age into account.

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.

Teenage Pregnancies in Austria - an Epidemiological Study on Prevalence and Perinatal Outcome.

Introduction Even though teenage pregnancy rates have been declining in the last decades, their global prevalence is still high and shows country-specific discrepancies. Insufficient sexual education, poor availability of contraceptives and early marriage are some of the multifactorial causes for adolescent pregnancies. Very often teenage pregnancies are classified as high-risk pregnancies. Studies have found higher rates of peripartal complications, such as preterm birth, low birth weight or low fetal Apgar-Scores. The aim of this retrospective cohort study is to evaluate the prevalence of teenage pregnancies in Austria and to identify principal differences in maternal and neonatal outcome. Material and methods Data were collected from the Austrian Birth Registry between 01/2012 and 12/2020. A total of 751661 deliveries in Austria were documented. Obstetric, maternal and neonatal parameters were descriptively analyzed. Mothers were subclassified into two age groups: teenage mothers of 19 years and younger and adult mothers of 20 to 39 years of age. Results Newborns of teenage mothers were significantly smaller (49.98 ± 3.11 vs. 50.31 ± 3.16 cm, p < 0.001) and had a lower birth weight (3216 ± 564 vs. 3247 ± 576 g, p < 0.001) than newborns of adult mothers. The percentage of caesarean deliveries in the teenage group was significantly lower than in adult mothers (21.1 vs. 31.8%, p < 0.001). Newborns of teenage mothers had significantly higher rates of very low (< 4) and low (< 7) 5-minute Apgar scores (5-minute Apgar < 4: 0.75 vs. 0.54%, p = 0.004) (5-minute Apgar < 7: 1.77 vs. 1.37%, p = 0.001) and significantly lower arterial umbilical-cord pH (7.25 ± 0.08 vs. 7.26 ± 0.08, p < 0.001). Perinatal mortality was higher in the age group below 20 years (0.7 vs. 0.6%, p = 0.043). Conclusion The data of this study show significantly poorer outcomes in pregnancies of teenagers compared to adult women, even though the healthcare system in Austria is considered excellent. Future guideline recommendations should focus on important aspects of obstetric care in teenage mothers.

Strategies for the prevention of maternal death from venous thromboembolism clinical recommendations based on current literature.

Venous thromboembolism (VTE) is one of the leading causes of direct maternal deaths. It has been estimated that approximately 50% of these deaths are potentially preventable. The UK Confidential Enquiries into Maternal Deaths and the National Partnership for Maternal Safety have proposed strategies for the prevention of maternal deaths from VTE based on current guideline recommendations. The main strategies include: - Early recognition and comprehensive assessment of risk factors for VTE at different times from the beginning of pregnancy until patient's discharge from hospital. - Appropriate risk stratification using standardized VTE risk assessment tools (e.g. the Royal College Scoring System). - Risk-based antenatal and postnatal heparin thromboprophylaxis adjusting the heparin dosage and the duration of prophylaxis to the individual patient's risk. - Adequate management of heparin prophylaxis before and after delivery. - Preference of universal rather than selective post-cesarean heparin thromboprophylaxis and application of perioperative mechanical prophylaxis. - Avoidance of gaps in the postpartum prescription of heparin. - Good communication and cooperation between primary and secondary care including community midwifery staff in the postpartum period. - Immediate intravenous administration of (unfractionated) heparin, if pulmonary embolism is suspected. - Critical analysis of all thromboembolic events, particularly in association with maternal death to learn from failures and to realize, if and where improvement is needed. Adequate pharmacological thromboprophylaxis has the potential to reduce the risk of VTE by 60-70% in pregnant women at increased risk.

Biomarker screening in preeclampsia: an RNA-sequencing approach based on data from multiple studies.

OBJECTIVE: Biomarkers have become important in the prognosis and diagnosis of various diseases. High-throughput methods, such as RNA sequencing facilitate the detection of differentially expressed genes (DEGs), hence potential biomarker candidates. Individual studies suggest long lists of DEGs, hampering the identification of clinically relevant ones. Concerning preeclampsia - a major obstetric burden with high risk for adverse maternal and/or neonatal outcomes - limitations in diagnosis and prediction are still important issues. We, therefore, developed a workflow to facilitate the screening for biomarkers. METHODS: On the basis of the tool DESeq2, a comprehensive workflow for identifying DEGs was established, analyzing data from several publicly available RNA-sequencing studies. We applied it to four RNA-sequencing datasets (one blood, three placenta) analyzing patients with preeclampsia and normotensive controls. We compared our results with other published approaches and evaluated their performance. RESULTS: We identified 110 genes that are dysregulated in preeclampsia, observed in at least three of the studies analyzed, six even in all four studies. These included FLT-1, TREM-1, and FN1, which either represent established biomarkers at protein level, or promising candidates based on recent studies. For comparison, using a published meta-analysis approach, 5240 DEGs were obtained. CONCLUSION: This study presents a data analysis workflow for preeclampsia biomarker screening, capable of identifying promising biomarker candidates, while drastically reducing the numbers of candidates. Moreover, we were also able to confirm its performance for heart failure. This approach can be applied to additional diseases for biomarker identification, and the set of DEGs identified in preeclampsia represents a resource for further studies.

Mechanical Methods for the Induction of Labour After Previous Caesarean Section - An Updated, Evidence-based Review.

There are currently no up-to-date evidence-based recommendations on the preferred method to induce labour after previous Caesarean section, especially for patients with unripe cervix, as randomised controlled studies are lacking. Intravenous oxytocin and misoprostol are contraindicated in these women because of the high risk of uterine rupture. In women with ripe cervix (Bishop Score > 6), intravenous administration of oxytocin is an effective procedure with comparable rates of uterine rupture to those with spontaneous onset of labour. Vaginal prostaglandin E 2 (PGE 2 ) and mechanical methods (balloon catheters, hygroscopic cervical dilators) are effective methods to induce labour in pregnant women with unripe cervix and previous Caesarean section. According to current guidelines, the administration of PGE 2 is associated with a higher rate of uterine rupture compared to balloon catheters. Balloon catheters are therefore a suitable alternative to PGE 2 to induce labour after previous Caesarean section, even though this is an off-label use. In addition to two meta-analyses published in 2016, 12 mostly retrospective cohort/observational studies with low to moderate levels of evidence have been published on mechanical methods of cervical ripening after previous Caesarean section. But because of the significant heterogeneity of the studies, substantial differences in study design, and insufficient numbers of pregnant women included in the studies, it is not possible to make any evidence-based recommendations based on these studies. According to a recent meta-analysis, the average rate using balloon catheters is approximately 53% and the average rate after spontaneous onset of labour is 72%. The uterine rupture rate was 0.2-0.9% for vaginal PGE 2 and 0.56-0.94% for balloon catheters and is therefore comparable to the uterine rupture rate associated with spontaneous onset of labour. According to the product informations, hygroscopic cervical dilators (Dilapan-S) are currently the only method which is not contraindicated for cervical ripening/induction of labour in women with previous Caesarean section, although data are insufficient. Well-designed, randomised, controlled studies with sufficient case numbers comparing balloon catheters and hygroscopic cervical dilators with mechanical methods and vaginal prostaglandin E 2 /oral misoprostol are therefore necessary to allow proper decision-making.

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.

Antibody Response and Maternofetal Antibody Transfer in SARS-CoV-2-Positive Pregnant Women: A Multicenter Observational Study.

Introduction Awareness of SARS-CoV-2 infection in pregnant women and the potential risk for infection of their neonates is increasing. The aim of this study was to examine the immune status of affected women and evaluate the dynamics of placental antibody transfer. Materials and Methods The study included 176 women with SARS-CoV-2 infection during pregnancy who delivered between April 2020 and December 2021 at eight obstetric maternity sites. Demographic data, maternal and neonatal characteristics were summarized. Antibody testing for IgA and IgG in maternal blood sera and umbilical cord samples was evaluated and IgG transfer ratios were calculated. Values were related to the time of infection during pregnancy and birth. Results The percentage of IgG positive women increased from 29.0% (95% CI 23.8 - 37.8) at presentation with a positive PCR test result to 75.7% (95% CI 71.6 - 79.8), the percentage of IgG positive umbilical cord blood samples increased from 17.1% (95% CI 13.0 - 21.3) to 76.4% (95% CI 72.2 - 80.7) at more than six weeks after infection. Regression lines differed significantly between maternal and fetal IgG responses (p < 0.0001). Newborns react with a latency of about one week; umbilical cord blood antibody concentrations are highly correlated with maternal concentration levels (ρ = 0.8042; p < 0.0001). IgG transplacental transfer ratios were dependent on infection-to-birth interval. Two of the umbilical cord blood samples tested positive for IgA. Conclusions These findings confirm vertical SARS-CoV-2 transmission is rare; however, antibodies are transferred to the fetus soon after infection during pregnancy. Since transplacental antibody transfer might have a protective value for neonatal immunization this information may be helpful when counseling affected women.

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.

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.

Amniotic-Umbilical-to-Cerebral Ratio - A Novel Ratio Combining Doppler Parameters and Amniotic Fluid Volume to Predict Adverse Perinatal Outcome in SGA Fetuses At Term.

PURPOSE: Introduction of a novel ratio - the amniotic-umbilical-to-cerebral ratio (AUCR) - to predict adverse perinatal outcome in SGA fetuses at term and comparison of its predictive accuracy with established parameters. MATERIALS AND METHODS: This retrospective cohort study included 165 singleton pregnancies with SGA fetuses (birth weight < 10th percentile) at term. Cases with planned vaginal delivery and documented pulsatility indices (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and single deepest pocket (SDP) were included. CPR was calculated as the ratio between MCA PI and UA PI, UCR as the ratio between UA PI and MCA PI. AUCR was defined as follows: SDP/(UA PI/MCA PI). Adverse perinatal outcomes were defined as operative intervention (OI), OI due to fetal distress, admission to the neonatal intensive care unit (NICU), and composite adverse perinatal outcome (CAPO). Associations between Doppler parameters and these outcomes were estimated using regression analyses. RESULTS: OI was statistically significantly associated with UCR, SDP, and AUCR, whereas no association was observed for UA PI, MCA PI, and CPR. Fetuses requiring OI due to fetal distress revealed a significantly higher UA PI and UCR as well as a lower MCA PI, CPR, and AUCR. With regard to NICU admission and CAPO, a significantly higher UA PI and lower CPR were found. Furthermore, a significant association was shown for SDP, UCR, and AUCR. AUCR achieved the best area under the curve for all outcome parameters. CONCLUSION: AUCR leads to an improvement in the prediction of unfavorable outcome in SGA fetuses at term. Furthermore, results of our study show that UCR might be superior to CPR.

Influence of Sonographic Fetal Weight Estimation Inaccuracies in Macrosomia on Perinatal Outcome.

OBJECTIVE: To evaluate the influence of inaccurate sonographic fetal weight estimation in macrosomia on the mode of delivery and neonatal outcome (NO). METHODS: In 14 633 pregnancies between 2002 and 2016, this retrospective study evaluated the association between sonographic fetal weight estimation, true birth weight (BW), mode of delivery (primary cesarean section [pCS], secondary cesarean section, vaginal delivery, and operative vaginal delivery rates) and NO parameters (5-min Apgar < 7, pH < 7.1, neonatal intensive care unit [NICU] admission, shoulder dystocia). Singleton pregnancies > 37 + 0 weeks with ultrasound-estimated fetal weight (EFW) within 7 days before delivery were included. The study population was divided into four groups: Group 1 (false-negative): EFW < 4000 g/BW ≥ 4000 g; Group 2 (true-positive): EFW ≥ 4000 g/BW ≥ 4000 g; Group 3 (false-positive): EFW ≥ 4000 g/BW < 4000 g; and Group 4 (true-negative): EFW < 4000 g/BW < 4000 g. RESULTS: As expected, the highest secondary cesarean section (sCS) rate was found in Group 2 (true-positive) (30.62 %), compared with only 17.68 % in Group 4 (true-negative). The sCS rate in the false-positive Group 3 was significantly higher (28.48 %) in comparison with the false-negative Group 1 (21.22 %; OR 1.48; 95 % CI, 1.16 to 1.89; P = 0.002). In comparison with the true-negative Group 4, univariate analyses showed significantly higher rates for sCS in all other groups: odds ratio (OR) 2.06 for Group 2 (95 % CI, 1.74 to 2.42; P < 0.001), 1.85 for Group 3 (95 % CI, 1.54 to 2.22, P < 0.001), and 1.25 for Group 1 (95 % CI, 1.05 to 1.49; P < 0.01). No significant differences were found for NO between Groups 1 and 3 for the parameters 5-min Apgar < 7 (P = 0.75), pH < 7.1 (P = 0.28), or NICU admission (P = 0.54). However, there was a significantly higher chance for shoulder dystocia in Group 1 compared with Group 3 (OR 4.58; 95 % CI, 1.34 to 24.30; P = 0.008). CONCLUSION: Sonographic EFW inaccuracies in fetal macrosomia appear to have a greater impact on the mode of delivery than birth weight itself. Underestimation of fetal weight may be associated with a higher probability of shoulder dystocia.

TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion.

Successful implantation requires the coordinated migration and invasion of trophoblast cells from out of the blastocyst and into the endometrium. This process relies on signals produced by cells in the maternal endometrium. However, the relative contribution of stroma cells remains unclear. The study of human implantation has major technical limitations, therefore the need of in vitro models to elucidate the molecular mechanisms. Using a recently described 3D in vitro models we evaluated the interaction between trophoblasts and human endometrial stroma cells (hESC), we assessed the process of trophoblast migration and invasion in the presence of stroma derived factors. We demonstrate that hESC promotes trophoblast invasion through the generation of an inflammatory environment modulated by TNF-α. We also show the role of stromal derived IL-17 as a promoter of trophoblast migration through the induction of essential genes that confer invasive capacity to cells of the trophectoderm. In conclusion, we describe the characterization of a cellular inflammatory network that may be important for blastocyst implantation. Our findings provide a new insight into the complexity of the implantation process and reveal the importance of inflammation for embryo implantation.

Labour Induction with Misoprostol in German Obstetric Clinics: What Are the Facts on Such Use?

Subject While the synthetic prostaglandin E1 analogue misoprostol is the most effect labour induction agent, its use is off-label for the most part. For this reason, and in view of its potential adverse effects and varying approaches to its administration, the drug has recently once again become a focus of critical attention. The objective of this survey was thus to establish a record of labour induction with misoprostol in German clinics and determine the impact of the negative reporting on everyday obstetric practice. Material and Methods In this cross-sectional study, 635 obstetrics and gynaecology departments in Germany were requested by email to participate in our survey in February/March 2020. Online responses to 19 questions were requested regarding the clinic, use of misoprostol before and after the critical reporting, use of misoprostol (sourcing, method of administration, dosage, monitoring) and other labour induction methods. Results A total of 262 (41.3%) of the clinics solicited for the survey completed the questionnaire. There were no differences regarding the care level (Perinatal Centre Level I, Perinatal Centre Level II, Clinic with Perinatal Focus or Obstetric/Private Clinic; p = 0.2104) or birth counts (p = 0.1845). In most cases, misoprostol was prepared in the clinic's own pharmacy (54%) or imported from another country (46%) and administered orally in tablet form (95%). Misoprostol dosage levels varied (25 µg [48%], 50 µg [83%], 75 µg [6%], 100 µg [47%] and > 100 µg [5%]). Most of the clinics used premanufactured tablets/capsules (59%), although Cytotec tablets were also divided (35%) or dissolved in water (5%). Misoprostol administration intervals were mainly every 4 hours (64%) or every 6 hours (30%). CTG checks were run in most cases before and after administration of a dose of misoprostol (78% and 76%) and before and after administration of a dose of prostaglandin E2 (both 88%). Presence of contractions led to no misoprostol (59%) or no prostaglandin E2 (64%) being administered in most cases. The critical reporting resulted in discontinuation of use of misoprostol in 17% of the clinics - mainly smaller obstetric/private clinics with fewer than 1000 births. Labour cocktails were used mainly in obstetric and private clinics (61%). Conclusion Misoprostol is an established agent for labour induction in German clinics. The dosing schemes used vary. Improvements of currently common management practices are required, especially in the area of labour induction (CTG checks before and after administration of labour-inducing medication, no administration of prostaglandin if contractions are ongoing). The discussion of use of misoprostol in the media resulted in stoppage of its use mainly in smaller clinics.