Maritta Kühnert

The prediction of fetal acidosis by means of intrapartum fetal pulse oximetry

OBJECTIVES The studys objectives were to verify a threshold value for fetal arterial oxygen saturation as the critical boundary for fetal compromise during labor and to investigate a method of predicting acidosis caused by hypoxemia. STUDY DESIGN In a multicenter study involving 3 German obstetric centers, a total of 400 deliveries were monitored by fetal pulse oximetry (Nellcor-Puritan-Bennett Model N-400 Oxygen Saturation Monitor and FS-14 Sensor; Nellcor, Inc, Pleasanton, Calif). The durations of low (</=30%), medium (31%-60%), and high (>60%) fetal arterial oxygen saturations during the measurement were compared between neonates with a pH <7.15 versus >/=7.15 and a base excess <-12 mmol/L versus >-12 mmol/L in the umbilical artery post partum and in neonates with an Apgar score <7 versus >/=7 by Mann-Whitney U test. In 121 of the pulse oximetry measurements the durations of low, medium, and high fetal arterial oxygen saturations were measured from one fetal scalp blood sampling to the next and correlated with the change of scalp blood pH between samplings. Multiple regression analysis was performed to estimate the expected change of pH between 2 fetal scalp blood samplings, and receiver operating characteristic analysis was done to define a minimum duration of low fetal arterial oxygen saturation values to exclude or predict a significant decline of pH. RESULTS Neonates with a 1-minute Apgar score <7 differed from those with 1-minute Apgar score >/=7 significantly in the duration of low fetal arterial oxygen saturation but not in the durations of medium and high fetal arterial oxygen saturations. The duration of low fetal arterial oxygen saturation had been significantly longer in children with pH <7.15 or base excess <-12 mmol/L in the umbilical artery compared with those with a pH >/=7.15 or base excess >/=-12 mmol/L. The duration of high fetal arterial oxygen saturation was significantly shorter for children with a pH <7.15 or base excess <12 mmol/L than for those with a pH >/=7.15 or base excess >/=12 mmol/L. There was no difference in the groups with respect to the duration of medium fetal arterial oxygen saturation values. The duration of low fetal arterial oxygen saturation proved to be the best predictor of a decline of scalp pH between 2 fetal scalp blood samples. The pH declined significantly with a longer duration of low fetal arterial oxygen saturation (0.02 per 10 minutes). No decrease of pH by more than 0.05 was observed unless fetal arterial oxygen saturation had remained at </=30% for >/=10 minutes. CONCLUSION An arterial oxygen saturation of 30% was confirmed as the critical boundary for fetal compromise during labor. The development of acidosis seems to be predictable by the duration of hypoxemia, as indicated by fetal arterial oxygen saturation </=30%.

Evaluation of quantitative ultrasound tissue characterization of the cervix and cervical length in the prediction of premature delivery for patients with spontaneous preterm labor.

OBJECTIVE This study was to evaluate the predictive value of the uterine cervix tissue with the use of quantitative ultrasound gray level analysis for preterm delivery. STUDY DESIGN Sixty-eight patients with preterm labor between 20 and 35 weeks of gestation were included. When two-dimensional transvaginal ultrasound measurement of cervical length was completed, a region of interest of constant size was defined in the midsection of the posterior wall, and the tissue-specific gray scale was determined. Preterm delivery of <37 weeks of gestation was sought. RESULTS Twenty-eight patients (41.2%) were delivered preterm. The risk for preterm delivery was increased significantly in patients with cervical length of </=2.5 cm (odds ratio, 7.67; 95% CI, 2.4-24.45), with Bishop score of >/=4 (odds ratio, 3.44; 95% CI, 1.21-9.75), and with decreased mean gray scale value (odds ratio, 12.13; 95% CI, 3.69-39.88). Parity and uterine contractions were not significant as predictors for preterm delivery, although the risk for preterm delivery increased with higher parity (odds ratio, 1.8; 95% CI, 0.68-4.79). The risk for preterm delivery remained nearly the same by uterine contractions (odds ratio, 0.92; 95% CI, 0.28-3.01). A mean scale value of </=6.54 had the best cutoff value for the prediction of preterm delivery. For preterm delivery, a mean gray value </=6.54 had a sensitivity of 82.1%, a specificity of 72.5%, a positive predictive value of 67.6%, and a negative predictive value 85.3%. Multiple logistic regression analysis indicated that, even when other variables are considered simultaneously, the mean gray scale value is the single best predictor of preterm delivery. CONCLUSION Quantitative ultrasound tissue characterization of the uterine cervix predicts premature delivery and provides additional information in the prediction of potential premature delivery.

Meta-analysis of studies on biochemical marker tests for the diagnosis of premature rupture of membranes: comparison of performance indexes

BackgroundPremature rupture of the membranes (PROM) is most commonly diagnosed using physical examination; however, accurate decision making in ambiguous cases is a major challenge in current obstetric practice. As this may influence a woman’s subsequent management, a number of tests designed to assist with confirming a diagnosis of PROM are commercially available. This study sought to evaluate the published data for the accuracy of two amniotic fluid-specific biomarker tests for PROM: insulin-like growth factor binding protein-1 (IGFBP-1 – Actim® PROM) and placental alpha microglobulin-1 (PAMG-1 – AmniSure®).MethodsMain analysis included all PubMed referenced studies related to Actim® PROM and AmniSure® with available data to extract performance rates. To compare accuracy, a comparison of pooled indexes of both rapid tests was performed. Studies in which both tests were used in the same clinical population were also analysed. Membrane status, whether it was known or a suspected rupture, and inclusion or not of women with bleeding, were considered.ResultsAll the available studies published in PubMed up to April 2013 were reviewed. Data were retrieved from 17 studies; 10 for Actim® PROM (n = 1066), four for AmniSure® (n = 1081) and three studies in which both biomarker tests were compared directly. The pooled analysis found that the specificity and positive predictive value were significantly higher for AmniSure® compared with Actim® PROM. However, when 762 and 1385 women with known or suspected rupture of membranes, respectively, were evaluated, AmniSure® only remained significantly superior in the latter group. Furthermore, when the two tests were compared directly in the same study no statistically significant differences were observed. Remarkably, women with a history or evidence of bleeding were excluded in all four studies for AmniSure®, in two Actim® PROM studies and in two of the three studies reporting on both tests.ConclusionsNo differences were observed in the performance of the two tests in studies where they were used under the same clinical conditions or in women with known membrane status. Although AmniSure® performed better in suspected cases of PROM, this may need further analysis as exclusion of bleeding may not be representative of the real clinical presentation of women with suspected PROM.

The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women

BACKGROUND The combination of the qualitative fetal fibronectin test and cervical length measurement has a high negative predictive value for preterm birth within 7 days; however, positive prediction is poor. A new bedside quantitative fetal fibronectin test showed potential additional value over the conventional qualitative test, but there is limited evidence on the combination with cervical length measurement. OBJECTIVE The purpose of this study was to compare quantitative fetal fibronectin and qualitative fetal fibronectin testing in the prediction of spontaneous preterm birth within 7 days in symptomatic women who undergo cervical length measurement. STUDY DESIGN We performed a European multicenter cohort study in 10 perinatal centers in 5 countries. Women between 24 and 34 weeks of gestation with signs of active labor and intact membranes underwent quantitative fibronectin testing and cervical length measurement. We assessed the risk of preterm birth within 7 days in predefined strata based on fibronectin concentration and cervical length. RESULTS Of 455 women who were included in the study, 48 women (11%) delivered within 7 days. A combination of cervical length and qualitative fibronectin resulted in the identification of 246 women who were at low risk: 164 women with a cervix between 15 and 30 mm and a negative fibronectin test (<50 ng/mL; preterm birth rate, 2%) and 82 women with a cervix at >30 mm (preterm birth rate, 2%). Use of quantitative fibronectin alone resulted in a predicted risk of preterm birth within 7 days that ranged from 2% in the group with the lowest fibronectin level (<10 ng/mL) to 38% in the group with the highest fibronectin level (>500 ng/mL), with similar accuracy as that of the combination of cervical length and qualitative fibronectin. Combining cervical length and quantitative fibronectin resulted in the identification of an additional 19 women at low risk (preterm birth rate, 5%), using a threshold of 10 ng/mL in women with a cervix at <15 mm, and 6 women at high risk (preterm birth rate, 33%) using a threshold of >500 ng/mL in women with a cervix at >30 mm. CONCLUSION In women with threatened preterm birth, quantitative fibronectin testing alone performs equal to the combination of cervical length and qualitative fibronectin. Possibly, the combination of quantitative fibronectin testing and cervical length increases this predictive capacity. Cost-effectiveness analysis and the availability of these tests in a local setting should determine the final choice.

Changes in lymphocyte subsets during pregnancy and post-partum in cases of beginning eclampsia

Abstract Aims: The goal of the present retrospective study was to examine the peripheral blood lymphocytes for expression of phenotypic and activation markers concerning the development of hypertension in pregnancy. Methods: 16 women (aged 25–43 years; mean 35.1) developing hypertension in the third trimester (week 25–34) have had blood samples taken in the first (< 14 weeks), the second (week 14–23), the third trimester (week 24–35), in late pregnancy (week 36-termination of pregnancy) and within 1 week post-partum, The control group consisted of 16 age-matched pregnant healthy women, who underwent the same regime. All blood samples were taken in the morning, stored at room temperature and stained within 6 hours and measured within 24 hours. Kruskal-Wallis analysis of variance between both groups was done with multiple comparison according to Dunn. Results: Comparing both groups, the total white cell count was significantly increased in all pregnancies and post-partum. In case of hypertension in pregnancy the cell numbers of suppressor/cytotoxic (CD 8+) and CD 56+-activated T cells showed a significant increase in the first trimester (< 14 weeks) [p < 0.05] and decreased thereafter to normal values. In the second trimester (week 14–23) helper/inducer lymphocytes and CD 56+1/CD 3+ lymphocytes decreased in case of pre-ecclampsia and cytotoxic lymphocytes elevated [p < 0.05]. In the third trimester (week 24–35) there was no difference in both study groups and in late pregnancy (week 36-termination) there were only small differences without statistical significance. Within 1 week postnatal the value of Il-2 receptor T lymphocytes decreased in the group of pre-eclampsia in comparison to normal pregnancies [p < 0.05]. Conclusions: Regarding the major changes in activated T cells in both study groups no specific pattern of lymphocyte subsets in case of pre-eclampsia could be found in comparison to healthy pregnant women. Further investigations should focus on functional activation and / or suppression of the cellular immune system. Perhaps this could lead to a screening test for pre-eclampsia in future, which is non-invasive for the patient and economic for our social community because it might reduce medical costs.

MR-tomografische Veränderungen bei Präeklampsie und Eklampsie

BACKGROUND Pre-eclampsia affects 2% of pregnancies. This multisystem disorder is a major cause of maternal, foetal and neonatal mortality and morbidity. Neurological manifestations of eclampsia are headache, nausea, vomiting, cortical blindness and recurrent seizures. OBJECTIVE The purpose of this study was to determine whether the neurological symptoms correlate with MR imaging findings. RESULTS In a patient with eclamptic seizure and another one with blindness due to pre-eclampsia, the white matter hyperintensities on T (2)-weighted MR and FLAIRsequence images could be demonstrated in the occipital region and in the basal ganglia. Within 3-5 days all neurological symptoms and radiological abnormalities had resolved. CONCLUSION These cerebral lesions could be classified as posterior reversible encephalopathy syndrome (PRES) or as reversible leukoencephalopathy syndrome (PLES). Thus, MRI supports differential diagnosis regarding non pregnancy-related cerebral disease and can be helpful for therapy planning in cases of pre-eclampsia.

24 hour-CTG monitoring: comparison of normal pregnancies and pregnancies with placenta insufficiency.

Abstract Aims: Routinely antepartal CTG will be recorded for 30 minutes to obtain normal resting phases, a decrease of irregulatory due to hypoxia or to differentiate these from each other. In case of early onset of hypoxia first pathological findings might only be seen by chance in incidentally recorded CTG. The goal of this study was, if a continuous 24 hour-CTG will allow an earlier detection of beginning hypoxia in case of placental insufficiency compared to a routine CTG of 30 minutes. Methods: 21 normal pregnancies and 17 patients with placental insufficiency of ≥ 36 weeks had 24 hour-CTGs by means of telemetry. In both study groups fetal heart rate (FHR) tracing included a full qualitative and quantitative description. Comparison of the results of both groups was done to look for early signs of pathological findings concerning reduced fetal well-being. Results: In comparison to normal pregnancies patients with placental insufficiency had in 4.5% oscillation frequency type A and an increase of saltatory and silent oscillation. The number of accelerations and Dip 0 was significantly reduced as well as accelerations in combination with undulatory oscillation. Baseline tachycardia and bradycardia showed significantly increasing quantity. Conclusions: 24 hour-CTG is a good screening method to detect early onset of hypoxia in case of beginning placental insufficiency. The failure to find any clinically significant difference in the diurnal variation of both groups suggests, that less than 24 hour testing is required. 8 hour-CTG could be a compromise and a big help to detect a fetus at risk earlier.

Peripartum Haemorrhage, Diagnosis and Therapy. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 015/063, March 2016)

Purpose This is an official interdisciplinary guideline, published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG), the Austrian Society of Gynaecology and Obstetrics (OEGGG) and the Swiss Society of Gynaecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking countries and is backed by the German Society of Anaesthesiology and Intensive Medicine (DGAI), the Society of Thrombosis and Haemostasis Research (GTH) and the German Association of Midwives. The aim is to provide a consensus-based overview of the diagnosis and management of peripartum bleeding obtained from an evaluation of the relevant literature. Methods This S2k guideline was developed from the structured consensus of representative members of the various professional associations and professions commissioned by the Guideline Commission of the DGGG. Recommendations The guideline encompasses recommendations on definitions, risk stratification, prevention and management.

Die Dynamik des Thrombin-Antithrombin-III-Komplexes und der Prothrombinfragmente F1 + 2 sub partu mit und ohne Aprotiningabe

Fragestellung: Ziel der Arbeit war, ob durch einmalige Gabe von Aprotinin maximal 15 min. vor Partus Auswirkungen auf das Gerinnungssystem der Gebarenden entstehen und ob es diesbezuglich Unterschiede zwischen Spontanpartus und Sectio gibt. Ferner sollte untersucht werden, ob durch die Bestimmung von Thrombin-Antithrombin-III-Komplex (TAT-III) und Prothrombinfragmenten F1 + 2 sub partu eine Gerinnungsaktivierung und prathrombotische Stadien erkannt werden konnen. Patienten und Methoden: 84 Patientinnen im Alter von 15 - 44 Jahren wurden untersucht (41 Spontangebarende, 43 Sectiopatientinnen). Davon erhielten 30 Frauen nach schriftlicher Einwilligung und Randomisierung maximal 15 Min. vor Partus 1 Million KIE Aprotinin (Trasylol®) i. v. (15 Spontangebarende, 15 Sectiopatientinnen). Bestimmt wurden TAT-III-Komplex und Prothrombinfragmente F1 + 2, sowie Faktor VIII und partielle Thromboplastinzeit kurz vor, direkt nach Geburt des Kindes und 30 und 120 Minuten nach Losung der Plazenta. Ergebnisse: Bei Spontangebarenden konnte nach Plazentalosung ein signifikanter Anstieg des TAT-III-Komplexes und ein deutlicher Anstieg der Prothrombinfragmente F1 + 2 festgestellt werden, der bei den mit Aprotinin behandelten Patientinnen einen signifikant niedrigeren Verlauf zeigte. Der Konzentrationsanstieg des TAT-III-Komplexes und der Prothrombinfragmente F1 + 2 war bei Sectiopatientinnen deutlich geringer ausgepragt als bei Spontangebarenden und wurde durch Aprotinin nicht signifikant beeinflusst. Faktor VIII und partielle Thromboplastinzeit (PTT) zeigten in keiner Patientengruppe klinisch relevante Veranderungen unter der Geburt. Schlussfolgerung und Diskussion: Der durch die Geburt ausgeloste Verbrauch von Gerinnungs- und Fibrinolysefaktoren kann durch eine Aprotiningabe 10 - 18 Min. vor Partus reduziert werden. Hieraus konnte sich auch ein therapeutischer Ansatz ergeben (z. B. bei Praeklampsie, HELLP-Syndrom etc.). Objective: The aim of this study was to determine if aprotinin could affect postpartal fibrinolysis when given at the latest 15 min before delivery and if there is a difference between normal delivery and caesarean section. Furthermore we wanted to examine if the thrombin-antithrombin-III-complex (TAT-III) and prothrombin fragments F1 + 2 changed in the peripartal period and if prethrombotic stages could be recognized. Patients and Methods: 84 patients (15 - 44 years of age) have been examined (41 normal deliveries, 43 cesarean sections). After giving informed consent and randomization, 30 of these patients were administered 1 Mio KIE aprotinin (Trasylol®) at the latest 15 min before delivery (15 normal deliveries, 15 cesarean sections). The results of TAT-III, prothrombin fragments F1 + 2, factor VIII and partial thromboplastin-time (PTT) were collected shortly before and after delivery and 30 and 120 min after detachment of the placenta. Results: Normal deliveries without aprotinin showed a significant increase of TAT-III and an evident increase of prothrombin fragments F1 + 2. After administration of aprotinin this increase was significantly lower. The increase of TAT-III and prothrombin fragments F1 + 2 in patients with caesarean sections was evidently lower than in normal deliveries and was not influenced significantly by aprotinin. Factor VIII and partial thromboplastin time (PTT) showed no relevant changes in all study groups. Discussion and Conclusion: The consumption of coagulation and fibrinolysis factors induced by delivery of the child and detachment of the placenta can be reduced after administration of aprotinin given at the latest 10 - 18 min before partus. This could be used in therapy and prophylactic treatment in high-risk patients (e. g., pre-eclampsia, HELLP syndrome, etc.).

Führt der Einsatz der Fetalblutanalyse zu einer Verminderung vaginaloperativer Entbindungen? – Eine Auswertung anhand der Hessischen Perinatalstatistik (HEPE)

Fragestellung: Welche Aussagen konnen mithilfe der externen Qualitatssicherung uber die Auswirkungen der an geburtshilflichen Kliniken in ihrer Frequenz stark unterschiedlich gehandhabten Fetalblutanalyse getroffen werden? Methode: Als Datenquelle dient die Hessische Perinatalstatistik von 1990 bis 2000. Kliniken mit >500 Entbindungen pro Jahr mit insgesamt 311.970 Einlinge >=37. Schwangerschaftswoche werden in die Analyse einbezogen. Zur Auswertung werden die pro Jahr von einer Klinik durchgefuhrten Fetalblutanalysen herangezogen. Ergebnisse: Es werden in Bezug auf die Frequenz der durchgefuhrten Fetalblutanalyse 4 Gruppen unterschieden: 1. 18,9%, 2. 6,5%, 3. 2,3%, 4. 0,6%. Vaginaloperative Entbindungen treten mit 6,1% absoluter Haufigkeit in der Gruppe mit hoher Rate an Fetalblutanalysen auf. Es findet sich signifikant eine kontinuierliche Zunahme der vaginaloperativen Entbindungen in den Gruppen mit niedrigerer Rate an Fetalblutanalysen bis um 13%.(relatives Risiko). Fur die weiteren Merkmale „sekundare Sektio“, Nabelarterien-PH“, „Apgar 10 Minuten <8“, „Apgar 5 Minuten <8“, „Apgar 1 Minute <8“, „regelmasige Eigenatmung nach 1 Minute“ und „Maskenbeatmung“ zeigen sich keine eindeutigen kontinuierlichen Bezuge. Schlussfolgerung: Trotz aller Zuruckhaltung in der Interpreation perinatalstatistischer Daten ist eine inverse Relation von der Frequenz der Fetalblutanalysen und vaginaloperativer Entbindungen zu erwagen.