Publications by authors named "Sven Kehl"

83 Publications

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

Geburtshilfe Frauenheilkd 2021 Aug 9;81(8):955-965. Epub 2021 Aug 9.

Frauenklinik, Universitätsklinikum Erlangen, Erlangen, Germany.

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. 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. 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%). 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.
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http://dx.doi.org/10.1055/a-1538-2200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354357PMC
August 2021

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

Geburtshilfe Frauenheilkd 2021 Aug 9;81(8):922-939. Epub 2021 Aug 9.

Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe, Kiel, Germany.

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.
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http://dx.doi.org/10.1055/a-1386-3912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354365PMC
August 2021

Caesarean Section. Guideline of the DGGG, OEGGG and SGGG (S3-Level, AWMF Registry No. 015/084, June 2020).

Geburtshilfe Frauenheilkd 2021 Aug 9;81(8):896-921. Epub 2021 Aug 9.

Pränatalmedizin und Geburtshilfe im Perinatalzentrum, Medizinische Hochschule Hannover, Hannover, Germany.

This is an official S3-guideline of the German Society of Gynaecology and Obstetrics (DGGG), the Austrian Society of Gynaecology and Obstetrics (ÖGGG) and the Swiss Society of Gynaecology and Obstetrics (SGGG). The guideline contains evidence-based information and recommendations on indications, complications, methods and care associated with delivery by caesarean section for all medical specialties involved as well as for pregnant women. This guideline has adapted information and recommendations issued in the NICE Caesarean Birth guideline. This guideline also considers additional issues prioritised by the Cochrane Institute and the Institute for Research in Operative Medicine (IFOM). The evaluation of evidence was based on the system developed by the Scottish Intercollegiate Guidelines Network (SIGN). A multi-part nominal group process moderated by the AWMF was used to compile this S3-level guideline. Recommendations on consultations, indications and the process of performing a caesarean section as well as the care provided to the mother and neonate were drawn up.
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http://dx.doi.org/10.1055/a-1529-6141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354346PMC
August 2021

Induction of Labour. Guideline of the DGGG, OEGGG and SGGG (S2k, AWMF Registry No. 015-088, December 2020).

Geburtshilfe Frauenheilkd 2021 Aug 9;81(8):870-895. Epub 2021 Aug 9.

Klinik für Gynäkologie, St. Joseph Krankenhaus, Berlin Tempelhof, Berlin, Germany.

The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society of Gynaecology and Obstetrics (OEGGG) and the Swiss Society of Gynaecology and Obstetrics (SGGG) is to provide a consensus-based overview of the indications, methods and general management of induction of labour by evaluating the relevant literature. This S2k guideline was developed using a structured consensus process which included representative members from various professions; the guideline was commissioned by the guidelines commission of the DGGG, OEGGG and SGGG. The guideline provides recommendations on the indications, management, methods, monitoring and special situations occurring in the context of inducing labour.
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http://dx.doi.org/10.1055/a-1519-7713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354342PMC
August 2021

Maternal SARS-CoV-2 infection during pregnancy: possible impact on the infant.

Eur J Pediatr 2021 Aug 5. Epub 2021 Aug 5.

Department of Pediatrics, University of Erlangen-Nürnberg, Loschgestr. 15, 91054, Erlangen, Germany.

The risk and potential consequences of mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy are still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Two PCR-confirmed perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded. In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, drug use, or maternal disease during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants.Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as support COVID-19 vaccination recommendations for pregnant women. Trial registration number: NCT04741412. Date of registration: November 18, 2020 What is Known: •Materno-fetal transmission of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) during pregnancy has rarely been reported so far, but was demonstrated in isolated cases. What is New: •In a study of complete households with documented SARS-CoV-2 infection, including a cohort of pregnant women, we observed perinatal coronavirus transmission at a higher frequency than expected. •We also describe a newborn boy with an eye malformation reminiscent of rubella embryopathy but associated with early gestation SARS-CoV-2 infection of his mother. •A coronavirus-related embryopathy, reported here for the first time, is a finding that requires further investigation.
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http://dx.doi.org/10.1007/s00431-021-04221-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341836PMC
August 2021

The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration.

J Perinat Med 2021 Jul 15. Epub 2021 Jul 15.

Department of Obstetrics and Gynecology, Erlangen University Hospital, Erlangen, Germany.

Objectives: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination.

Methods: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU).

Results: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272).

Conclusions: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length.
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http://dx.doi.org/10.1515/jpm-2021-0048DOI Listing
July 2021

[Intrahepatic cholestasis of pregnancy].

Gynakologe 2021 Apr 20:1-16. Epub 2021 Apr 20.

Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universität Düsseldorf, Düsseldorf, Deutschland.

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.
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http://dx.doi.org/10.1007/s00129-021-04787-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056200PMC
April 2021

Recommendations of the AGG (Task Force for Obstetrics, Section Maternal Diseases) on the Management of Maternal Hepatitis B, C and D Infection in Pregnancy.

Geburtshilfe Frauenheilkd 2021 Apr 14;81(4):390-397. Epub 2021 Apr 14.

Gynäkologie und Geburtshilfe, Universitätsklinikum des Saarlandes, Homburg, Germany.

These statements and recommendations should provide appropriate information about maternal and fetal routes of infection, screening, detection of risk factors, diagnostic procedures, treatment, birth planning and peripartum and postpartum management of maternal hepatitis infection and offer pointers for prenatal counselling and routine clinical care on delivery wards.
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http://dx.doi.org/10.1055/a-1330-7514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046515PMC
April 2021

Outpatient Induction of Labor - Are Balloon Catheters an Appropriate Method?

Geburtshilfe Frauenheilkd 2021 Jan 19;81(1):70-80. Epub 2021 Jan 19.

Frauenklinik, Universitätsklinikum Erlangen, Erlangen, Germany.

As the number of labor inductions in high-income countries has steadily risen, hospital costs and the additional burden on obstetric staff have also increased. Outpatient induction of labor is therefore becoming increasingly important. It has been estimated that 20 - 50% of all pregnant women requiring induction would be eligible for outpatient induction. The use of balloon catheters in patients with an unripe cervix has been shown to be an effective and safe method of cervical priming. Balloon catheters are as effective as the vaginal administration of prostaglandin E or oral misoprostol. The advantage of using a balloon catheter is that it avoids uterine hyperstimulation and monitoring is less expensive. This makes balloon catheters a suitable option for outpatient cervical ripening. Admittedly, intravenous administration of oxytocin to induce or augment labor is required in approximately 75% of cases. Balloon catheters are not associated with a higher risk of maternal and neonatal infection compared to vaginal PGE . Low-risk pregnancies (e.g., post-term pregnancies, gestational diabetes) are suitable for outpatient cervical ripening with a balloon catheter. The data for high-risk pregnancies are still insufficient. The following conditions are recommended when considering an outpatient approach: strict selection of appropriate patients (singleton pregnancy, cephalic presentation, intact membranes), CTG monitoring for 20 - 40 minutes after balloon placement, the patient must be given detailed instructions about the indications for immediate readmission to hospital, and 24-hour phone access to the hospital must be ensured. According to reviewed studies, the balloon catheter remained in place between 12 hours ("overnight") and 24 hours. The most common reason for readmission to hospital was expulsion of the balloon catheter. The advantages of outpatient versus inpatient induction of cervical ripening with a balloon catheter were the significantly shorter hospital stay, the lower costs, and higher patient satisfaction, with both procedures having been shown to be equally effective. Complication rates (e.g., vaginal bleeding, severe pain, uterine hyperstimulation syndrome) during the cervical ripening phase are low (0.3 - 1.5%); severe adverse outcomes (e.g., placental abruption) have not been reported. Compared to inpatient induction of labor using vaginal PGE , outpatient cervical ripening using a balloon catheter had a lower rate of deliveries/24 hours and a significantly higher need for oxytocin; however, hospital stay was significantly shorter, frequency of pain during the cervical ripening phase was significantly lower, and patients' duration of sleep was longer. A randomized controlled study comparing outpatient cervical priming with a balloon catheter with outpatient or inpatient induction of labor with oral misoprostol would be of clinical interest.
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http://dx.doi.org/10.1055/a-1308-2341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815336PMC
January 2021

„Die Welt hat sich verändert …“.

Authors:
Sven Kehl

Z Geburtshilfe Neonatol 2020 Dec 4;224(6):325. Epub 2020 Dec 4.

Frauenklinik, Universitätsklinikum Erlangen.

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http://dx.doi.org/10.1055/a-1288-3415DOI Listing
December 2020

Influence of labor on direct and indirect determinants of placental 11beta-hydroxysteroid dehydrogenase activity.

Arch Gynecol Obstet 2021 02 3;303(2):401-408. Epub 2020 Sep 3.

Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander-University of Erlangen-Nuremberg, Loschgestr. 15, 91054, Erlangen, Germany.

Purpose: Labor is a complex process involving multiple para-, auto- and endocrine cascades. The interaction of cortisol, corticotropin-releasing hormone (CRH) and progesterone is essential. The action of cortisol on the human feto-placental unit is regulated by 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2/HSD11B2) that converts cortisol into inactive cortisone. The majority of studies on the assessment of placental 11β-HSD2 function determined indirect activity parameters. It remains elusive if indirect measurements correlate with enzymatic function and if these parameters are affected by potential confounders (e.g., mode of delivery). Thus, we compared determinants of indirect 11β-HSD2 tissue activity with its direct enzymatic turnover rate in placental samples from spontaneous births and cesarean (C)-sections.

Methods: Using LC-MS/MS, we determined CRH, cortisol, cortisone, progesterone and 17-hydroxy(OH)-progesterone in human term placentas (spontaneous birth vs. C-section, n = 5 each) and measured the enzymatic glucocorticoid conversion rates in placental microsomes. Expression of HSD11B1, 2 and CRH was determined via qRT-PCR in the same samples.

Results: Cortisol-cortisone ratio correlated with direct microsomal enzymatic turnover. While this observation seemed independent of sampling site, a strong influence of mode of delivery on tissue steroids was observed. The mRNA expression of HSD11B2 correlated with indirect and direct cortisol turnover rates in C-section placentas only. In contrast to C-sections, CRH, cortisol and cortisone levels were significantly increased in placental samples following spontaneous birth.

Conclusion: Labor involves a series of complex hormonal processes including activation of placental CRH and glucocorticoid metabolism. This has to be taken into account when selecting human cohorts for comparative analysis of placental steroids.
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http://dx.doi.org/10.1007/s00404-020-05755-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858211PMC
February 2021

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

Ultraschall Med 2020 Aug 6. Epub 2020 Aug 6.

Obstetrics and Gynecology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

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.
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http://dx.doi.org/10.1055/a-1205-0191DOI Listing
August 2020

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.

Ultraschall Med 2020 Jul 28. Epub 2020 Jul 28.

Obstetrics and Gynecology, Erlangen University Hospital, Erlangen, Germany.

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 < 10 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.
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http://dx.doi.org/10.1055/a-1205-0161DOI Listing
July 2020

Influence of Preeclampsia on Induction of Labor at Term: A Cohort Study.

In Vivo 2020 May-Jun;34(3):1195-1200

Department of Obstetrics and Gynecology, Erlangen University Hospital, Erlangen, Germany

Background/aim: Even though vaginal delivery is a feasible option in patients with preeclampsia, the cesarean section rate in those patients is high. The aim of this study was to evaluate the influence of preeclampsia on induction of labor at term.

Patients And Methods: This historical cohort study analyzed inductions of labor in women at term having preeclampsia versus women who were induced due to other reasons. The primary outcome measure was the cesarean section rate.

Results: The cesarean section rate was higher in the preeclampsia group for both nulliparous and multiparous women after induction of labor but failed to reach statistical significane. The induction-to-delivery interval was longer in nulliparous women and the rate of vaginal birth within 48 h was lower in the nulliparous patiens with preeclampsia. However, the impact of preeclampsia on the cesarean section rate was not significant in the multivariable analysis following adjustment for BMI and parity.

Conclusion: Preeclampsia at term did not influence the cesarean section rate in nulliparous and parous women when labor was induced.
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http://dx.doi.org/10.21873/invivo.11892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279832PMC
February 2021

SARS-CoV-2 Infection in Pregnancy - a Review of the Current Literature and Possible Impact on Maternal and Neonatal Outcome.

Geburtshilfe Frauenheilkd 2020 Apr 26;80(4):380-390. Epub 2020 Mar 26.

Universitätsklinikum Erlangen, Virologisches Institut, Erlangen, Germany.

In December 2019, cases of pneumonia of unknown cause first started to appear in Wuhan in China; subsequently, a new coronavirus was soon identified as the cause of the illness, now known as Coronavirus Disease 2019 (COVID-19). Since then, infections have been confirmed worldwide in numerous countries, with the number of cases steadily rising. The aim of the present review is to provide an overview of the new severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) and, in particular, to deduce from it potential risks and complications for pregnant patients. For this purpose, the available literature on cases of infection in pregnancy during the SARS epidemic of 2002/2003, the MERS (Middle East respiratory syndrome) epidemic ongoing since 2012, as well as recent publications on cases infected with SARS-CoV-2 in pregnancy are reviewed and reported. Based on the literature available at the moment, it can be assumed that the clinical course of COVID-19 disease may be complicated by pregnancy which could be associated with a higher mortality rate. It may also be assumed at the moment that transmission from mother to child in utero is unlikely. Breastfeeding is possible once infection has been excluded or the disease declared cured.
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http://dx.doi.org/10.1055/a-1134-5951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174004PMC
April 2020

[Does Induction of Labor for Preterm Premature Rupture of Membranes at 34 Weeks of Gestation Increase the Risk for Cesarean Section?]

Z Geburtshilfe Neonatol 2020 Oct 2;224(5):269-274. Epub 2020 Mar 2.

Frauenklinik, Universitätsklinikum Erlangen, Erlangen.

Purpose: Induction of labor at 34 weeks of gestation is often linked to increased risk for cesarean section. Recently, the PPROMT trial demonstrated a higher cesarean section rate when labor was induced for preterm premature rupture of membranes (PPROM). The purpose of this study was therefore to evaluate the success rate of induction of labor for PPROM at 34 and 35 weeks of gestation in comparison with a higher gestational age.

Material And Methods: In this historic cohort study, cases with labor inductions for PPROM ≥ 34 weeks of gestation were included. Induction of labor at 34 and 35 weeks of gestation (group 1) were compared with those performed at 36 weeks (group 2) and 37 weeks (group 3). Induction of labor was started 12 to 24 hours after (preterm) premature rupture of membranes. Antibiotics were given routinely. The primary outcome was the rate of cesarean section.

Results: There were significantly more cesarean sections in group 3 in comparison with group 2 (7 vs. 25%, p=0.0136). However, univariable and multiple logistic regression analysis of the primary outcome measure showed that there was no impact of the group affiliation on cesarean section rate. Significant parameters influencing the risk of cesarean section were body mass index and Bishop score.

Conclusion: Induction of labor for PPROM at 34 weeks of gestation is not associated with an increased rate of cesarean section.
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http://dx.doi.org/10.1055/a-1110-1132DOI Listing
October 2020

Maintenance tocolysis: a reappraisal of clinical evidence.

Arch Gynecol Obstet 2019 11 1;300(5):1189-1199. Epub 2019 Oct 1.

Medizinische Fakultät Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Introduction: Maintenance tocolysis, mostly defined as the continuation of tocolytic treatment beyond 48 h, remains a matter of debate. There is no sufficient evidence from randomized controlled trials, that maintenance tocolysis is able to prolong pregnancy significantly and to reduce severe neonatal morbidity and mortality. Hence, it is not recommended in current guidelines. On the contrary, maintenance tocolysis is commonly used in clinical practice and subject of current clinical-scientific investigations.

Tocolytics For Maintenance Treatment: None of the conventional tocolytics (beta-sympathomimetics, calcium-channel blockers, magnesium, cyclooxygenase inhibitors, and oxytocin receptor antagonists) have proven to be appropriate for maintenance treatment. Progesterone and 17-α-hydroxyprogesterone caproate have shown promising results in low-quality randomized trials, but not in high-quality studies.

Discussion: Basically, the value of studies regarding maintenance tocolysis is limited by a considerable heterogeneity, its mostly low quality, significant differences in methodology as well as the inadequate statistical power due to the small number of women studied. So far, maintenance tocolysis is a case-by-case decision outweighing the benefits and harms of tocolytic treatment.
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http://dx.doi.org/10.1007/s00404-019-05313-7DOI Listing
November 2019

Ultrasound Fetal Weight Estimation in Diabetic Pregnancies.

J Ultrasound Med 2020 Feb 22;39(2):341-350. Epub 2019 Aug 22.

Department of Obstetrics and Gynecology, Erlangen University Hospital, Erlangen, Germany.

Objectives: To evaluate different formulas for estimating fetal weight in diabetic pregnancies.

Methods: This retrospective study evaluated the precision of ultrasound fetal weight estimation in 756 pregnancies complicated by gestational diabetes between 2002 and 2016. The estimated fetal weights (EFWs) were obtained within 7 days of delivery from 10 weight estimation formulas and were compared with pair-wise matched controls from 15,701 patients. The precision of the evaluated formulas for EFW was analyzed by median absolute percentage errors (MAPEs), mean percentage errors (MPEs), and proportions of estimates within 10% of actual birth weight.

Results: Among the tested formulas, the lowest MAPE was detected with formula I of Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337), and the formula of Schild et al (Ultrasound Obstet Gynecol 2004; 23:30-35) had the highest proportion of estimates within the 10% range. The EFW in diabetic patients showed a slight trend toward overestimation in comparison with the matched controls (MPE estimates showed a trend toward more positive values). In most of the EFW formulas that were evaluated, no significant differences were detected in MAPEs and estimates within the 10% range. The MPE estimates with most formulas in both groups were close to zero. Overall, the differences between most of the evaluated formulas were small.

Conclusions: Little evidence was found for differences in the accuracy of the EFW in diabetic pregnancies and controls. The Hadlock I formula showed the lowest MAPE, and the Schild formula had the highest proportion of estimates within the 10% range.
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http://dx.doi.org/10.1002/jum.15112DOI Listing
February 2020

Induction of labour with sequential double-balloon catheter and oral misoprostol versus oral misoprostol alone in obese women.

Eur J Obstet Gynecol Reprod Biol X 2019 Jul 1;3:100034. Epub 2019 May 1.

Department of Obstetrics and Gynaecology, Erlangen University Hospital, Germany.

Objective: To evaluate the efficacy of induction of labour in obese women using sequential double-balloon catheter and oral misoprostol in comparison with oral misoprostol alone.

Study Design: In this cohort study, 400 pregnant women with BMI higher than 35 kg/m2 undergoing labour induction at term were included. Induction of labour with a double-balloon catheter and, if necessary, sequential oral misoprostol (n = 216) was compared to oral misoprostol alone (n = 184). The primary outcome measure was the caesarean section rate. Secondary outcome parameters were, among others, the induction-to-delivery-interval, the rate of vaginal delivery within 24 and 48 h as well as fetal outcome parameters.

Results: The caesarean section rate was significantly lower in the group with sequential use of double-balloon catheter and oral misoprostol (27.6% versus 37.5%, p = 0.0345). After stratification for parity this reduction was seen especially in nulliparous (38.6% versus 56.9%, p = 0.0039). The rate of abnormal CTG was significantly lower as well (19.9% versus 30.4%, p = 0.0150), particularly in nulliparous (25.9% versus 40.4%, p = 0.0138). Uni- and multivariable analyzes showed that the caesarean section rate was significantly influenced by the method of induction of labour (p = 0.0026), parity (p < 0.0001) and Bishop score (p = 0.0425).

Conclusion: In obese women, induction of labour with sequential use of double-balloon catheter and oral misoprostol is associated with significantly more normal vaginal deliveries and less caesarean sections.
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http://dx.doi.org/10.1016/j.eurox.2019.100034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687443PMC
July 2019

Longitudinal Course of Short-Term Variation and Doppler Parameters in Early Onset Growth Restricted Fetuses.

Ultraschall Med 2020 Dec 25;41(6):e23-e32. Epub 2019 Jun 25.

Obstetrics and Gynecology, University-Hospital of Erlangen, Germany.

Purpose:  To evaluate the longitudinal pattern of fetal heart rate short term variation (STV) and Doppler indices and their correlation to each other in severe growth restricted (IUGR) fetuses.

Materials And Methods:  In this retrospective study, pregnancies with a birth weight below the 10th percentile, born between 24 and 34 gestational weeks with serial Doppler measurements in combination with a computerized CTG (cCTG) with calculated STV were included. Longitudinal changes of both Doppler indices and STV values were evaluated with generalized additive models, adjusted for gestational age and the individual. For all measurements the frequency of abnormal values with regard to the time interval before delivery and Pearson correlations between Doppler indices and STV values were calculated.

Results:  41 fetuses with a total of 1413 observations were included. Over the course of the whole study period, regression analyses showed no significant change of STV values (p = 0.38). Only on the day of delivery, a prominent decrease was observed (mean STV d28-22: 7.97 vs. mean STV on day 0: 6.8). Doppler indices of UA and MCA showed a continuous, significant deterioration starting about three weeks prior to delivery (p = 0.007; UA and p < 0.001, MCA). Correlation between any Doppler index and STV values was poor.

Conclusion:  Fetal heart rate STV does not deteriorate continuously. Therefore, cCTG monitoring should be performed at least daily in these high-risk fetuses. Doppler indices of umbilical artery (UA) and middle cerebral artery (MCA), however, showed continuous deterioration starting about 3 weeks prior to delivery.
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http://dx.doi.org/10.1055/a-0858-2290DOI Listing
December 2020

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in small-for-gestational age fetuses at term.

Arch Gynecol Obstet 2019 09 17;300(3):575-581. Epub 2019 Jun 17.

Department of Obstetrics and Gynecology, University Hospital of Erlangen, Universitätsstraße 21/23, 91054, Erlangen, Germany.

Objective: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in small-for-gestational-age (SGA) fetuses at term.

Methods: In this retrospective single-center study 97 patients with singleton SGA fetuses at term (≥ 37 + 0 weeks' gestation) were examined. Inclusion criteria were a birth weight < 10th centile, cephalic presentation and planned vaginal birth. Only cases with available Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) with calculated cerebroplacental ratio (CPR) in combination with a computerized CTG (cCTG) and STV 72 h prior to delivery were eligible for analysis. Pulsatility indices (PI) were converted into multiples of median (MoM), adjusted for gestational age. The association between Doppler indices and STV values with mode of delivery [secondary cesarean delivery (CD), operative vaginal delivery (OVD), as well as secondary CD and OVD due to fetal distress] and neonatal outcome [UA blood pH ≤ 7.15 and the need of admission to the neonatal intensive care unit (NICU)] was analyzed using logistic regression analysis.

Results: There was a significant association between UA PI MoM and the rate of CD. CD due to fetal distress, OVD and OVD due to fetal distress did not show a correlation with the evaluated Doppler parameters. Furthermore, we did not find an association between low UA birth pH and Doppler parameters while neonates with the need of admission to NICU had significant higher UA PI MoM and significant lower MCA PI MoM and CPR MoM. Regarding STV, a significant effect of low STV on NICU admission was found while none of the other assessed outcome parameters were significantly associated with STV.

Conclusion: STV and Doppler parameters in SGA fetuses at term are significantly associated to the rate of NICU admission.
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http://dx.doi.org/10.1007/s00404-019-05216-7DOI Listing
September 2019

Induction of Labour in Growth Restricted and Small for Gestational Age Foetuses - A Historical Cohort Study.

Geburtshilfe Frauenheilkd 2019 Apr 12;79(4):402-408. Epub 2019 Apr 12.

Frauenklinik, Universitätsklinikum Erlangen, Erlangen, Germany.

Induction of labour for small-for-gestational-age (SGA) foetus or intrauterine growth restriction (IUGR) is common, but data are limited. The aim of this study was therefore to compare labour induction for SGA/IUGR with cases of normal foetal growth above the 10th percentile. This historical multicentre cohort study included singleton pregnancies at term. Labour induction for SGA/IUGR (IUGR group) was compared with cases of foetal growth above the 10th percentile (control group). Primary outcome measure was caesarean section rate. The caesarean section rate was not different between the 2 groups (27.0 vs. 26.2%, p = 0.9154). In the IUGR group, abnormal CTG was more common (30.8 vs. 21.9%, p = 0.0214), and foetal blood analysis was done more often (2.5 vs. 0.5%, p = 0.0261). There were more postpartum transfers to the NICU in the IUGR group (40.0 vs. 12.8%, p < 0.0001), too. Induction of labour for foetal growth restriction was not associated with an increased rate of caesarean section.
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http://dx.doi.org/10.1055/a-0834-8199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461466PMC
April 2019

Acute Tocolysis - a Critical Analysis of Evidence-Based Data.

Geburtshilfe Frauenheilkd 2018 Dec 14;78(12):1245-1255. Epub 2018 Dec 14.

Frauenklinik, Universitätsklinikum Erlangen, Erlangen, Germany.

Tocolysis is among the most common obstetric measures. The objective is to prolong the pregnancy by at least 48 hours to complete foetal lung maturation and for the in-utero transfer of the pregnant woman to a perinatal centre. The indication for tocolysis is regular, premature contractions (≥ 4/20 min) and a dynamic shortening of the cervical length/cervical opening between 22 + 0 to 33 + 6 weeks of pregnancy. In this connection, the cervical length measured on ultrasound and the determination of biomarkers in the cervicovaginal secretions can be important decision-making aids. Beta sympathomimetics should no longer be used due to the high rate of severe maternal adverse effects. Given controversial data, magnesium sulphate is no longer recommended for tocolysis in current guidelines. Atosiban is as effective for prolonging pregnancy as beta sympathomimetics and nifedipine, has the lowest rate of maternal adverse effects, but also the highest drug costs. Nifedipine and indomethacin are recommended in international guidelines for acute tocolysis, however there are indications of increased neonatal morbidity following indomethacin. Current problems are, above all, the lack of randomised, controlled comparative and placebo-controlled studies, the data which are controversial to some extent, and the insufficient evidence of tocolytics to significantly improve the neonatal outcome.
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http://dx.doi.org/10.1055/a-0717-5329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294642PMC
December 2018

[Induction of Labour In Growth Restricted and Small for Gestational Age Fetuses - A Historical Cohort Study].

Z Geburtshilfe Neonatol 2019 Feb 16;223(1):40-47. Epub 2019 Jan 16.

Frauenklinik, Universitätsklinikum Erlangen, Erlangen.

Purpose: Induction of labour for small-for-gestational-age (SGA) foetus or intrauterine growth restriction (IUGR) is common, but data are limited. The aim of this trial was therefore to compare labour induction for SGA/IUGR with cases with normal fetal growth beyond the 10 percentile.

Material And Methods: This historical multicentre cohort study included singleton pregnancies at term. Labour induction for SGA/IUGR (IUGR group) was compared with cases of fetal growth beyond the 10 percentile (control group). Primary outcome measure was caesarean section rate.

Results: The caesarean section rate was not different between the 2 groups (27.0 vs. 26.2%, p=0.9154). In the IUGR group, abnormal CTG was more common (30.8 vs. 21.9%, p=0.0214), and fetal blood analyses were conducted more often (2.5 vs. 0.5%, p=0.0261). There were more postpartum transfers to the NICU in the IUGR group (40.0 vs. 12.8%, p<0.0001), too.

Conclusion: Induction of labour for fetal growth restriction was not associated with an increased rate of caesarean section.
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http://dx.doi.org/10.1055/a-0809-6110DOI Listing
February 2019

Correlation of short-term variation and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term.

Arch Gynecol Obstet 2019 02 3;299(2):411-420. Epub 2018 Dec 3.

Department of Obstetrics and Gynecology, Erlangen University Hospital, Universitätsstraße 21-23, 91054, Erlangen, Germany.

Objective: To evaluate the association of short-term variation (STV) and Doppler parameters with adverse perinatal outcome in low-risk fetuses at term.

Methods: This was a retrospective study of 1008 appropriate-for-gestational age (AGA) term fetuses. Doppler measurements [umbilical artery (UA), middle cerebral artery (MCA), and cerebroplacental ratio (CPR)] and computerized CTG (cCTG) with STV analysis were performed prior to active labor (≤ 4 cm cervical dilatation) within 72 h of delivery. The association between Doppler indices and STV values with adverse perinatal outcome was analyzed using univariate regression analysis.

Results: No significant association between Doppler parameters and the need for secondary cesarean delivery (CD) or operative vaginal delivery (OVD) was shown. Regarding fetuses delivered by CD due to fetal distress, regression analyzes revealed significantly higher UA PI MoM. However, the differences in MCA PI MoM and CPR MoM were not statistically significant. Fetuses with the need for emergency CD showed significantly higher UA PI MoM, lower MCA PI MoM and lower CPR MoM. Neonates with a 5-min Apgar score < 7 had significantly lower MCA PI MoM and neonatal acidosis (UA pH ≤ 7.10) showed a significant association with UA PI MoM. None of the assessed outcome parameters were significantly associated to STV.

Conclusion: Doppler indices assessed close to delivery in low-risk fetuses at term show a moderate association with adverse outcome parameters, whereas STV does not appear to predict poor perinatal outcome in this group of fetuses.
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http://dx.doi.org/10.1007/s00404-018-4978-zDOI Listing
February 2019

Can Sonographic Fetal Biometry Predict Adverse Perinatal Outcome?

Ultraschall Med 2019 Apr 5;40(2):230-236. Epub 2018 Nov 5.

Obstetrics and Gynecology, University Hospital of Erlangen, Germany.

Objective:  To evaluate the association of sonographic fetal biometry (sonographic head circumference (soHC), sonographic abdominal circumference (soAC), estimated fetal weight (EFW)) with mode of delivery and adverse perinatal outcome.

Methods:  Singleton pregnancies with a gestational age ≥ 37 weeks and an ultrasound examination with complete biometric parameters within 7 days before delivery were retrospectively included. The association between soHC, soAC, EFW and fetal (5-min Apgar < 7, pH < 7.1, neonatal intensive care unit (NICU) admission, shoulder dystocia (ShD)) and maternal (obstetric intervention (OI): caesarean or vaginal operative delivery, obstetric anal sphincter injury syndrome (OASIS), postpartum hemorrhage (pph)) adverse outcomes were analyzed using univariate and multivariate logistic regression analyses.

Results:  12 396 women were included and 3479 (28.07 %) needed an OI. Multivariate analyses demonstrated significant contributions for the prediction of OI by soHC and soAC, whereas EFW did not reach significance. The highest OR was shown for soHC (1087, p < 0.001). ShD occurred in 73 (0.59 %) of the deliveries. Multivariate analyses showed that significant contributions for the prediction of ShD were provided only by soAC (OR 1460, p = 0.007). For the other maternal and neonatal adverse outcome parameters, no significant association with the biometric measurements could be demonstrated in the multivariate analyses. The overall detection rates for the prediction of adverse perinatal outcome by the different biometric parameters and EFW were poor.

Conclusion:  Obstetric management decisions should not be based solely on measurements of biometric parameters or EFW.
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http://dx.doi.org/10.1055/a-0576-0143DOI Listing
April 2019
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