Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study.

Objective: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design: International, prospective, multicentre cohort study. Setting: Six university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019. Participants: Low risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures: Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results: Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions: The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registration: ClinicalTrials.gov NCT02035059.

2D pelvic floor ultrasound imaging in identifying levator ani muscle trauma agrees highly with 4D ultrasound imaging.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the agreement between 2D and 4D translabial ultrasound (TLUS) technique in showing levator ani muscle (LAM) states after vaginal birth. METHODS: In a prospective observational cohort study between March 2017 and April 2019 we evaluated LAM states (intact, hematoma, partial, complete avulsion) of primiparous women having given birth vaginally with singletons in vertex presentation ≥ 36+0 gestational weeks by using 2D and 4D TLUS within 1-4 days postpartum (assessment A1) and again 6-10 weeks postpartum (assessment A2). Cohen's Kappa analysis was performed for each side separately to evaluate the test agreement between the two ultrasound techniques at every assessment period. RESULTS: A total of 224 women participated at A1 and 213 at A2. The agreement between the two ultrasound techniques was good to very good at A1 (Cohen`s kappa right-sided 0.78, left-sided 0.82) and very good at A2 (Cohen`s kappa both sides 0.88). The agreement was best when assessing an intact LAM or a complete avulsion (Cohen`s kappa between 0.78-0.92 for complete avulsions). CONCLUSIONS: The comparison between 2D and 4D TLUS showed a good to very good agreement in LAM trauma immediately after birth as well as 6-10 weeks postpartum. Therefore, 2D ultrasound could also be a valuable method for demonstrating a LAM abnormality and could be used in settings where 3D/4D ultrasound equipment is not available.

The evolution of levator ani muscle trauma over the first 9 months after vaginal birth.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the evolution of levator ani muscle (LAM) trauma over the first 9 months after birth and to evaluate their agreement between different assessment periods. METHODS: From March 2017 to April 2019 we prospectively evaluated LAM states (intact, hematoma, partial or complete avulsion) of primiparous women after vaginal birth by using 4D translabial ultrasound (TLUS) at three different assessment periods. All women were examined 1-4 days (A1) and 6-10 weeks (A2) postpartum, and women with a trauma additionally 6-9 months postpartum (A3). Cohen's Kappa analysis was performed to evaluate the test agreement between the assessment periods. RESULTS: Thirty-two percent of the women at A1 had a LAM trauma and 24% at A2. The higher number of LAM injuries at A1 can be explained by hematomas (14%), of which 51% spontaneously resolved at A2, 35% revealed themselves as partial, and 12% as complete avulsions. At A3, we observed anatomical improvement from complete to partial avulsions (23%) and few partial avulsions changed into an intact LAM (3%); none of the complete avulsions changed into an intact LAM. The agreement of 4D TLUS between A1 and A2 was moderate to good (0.64 for the right-sided LAM/0.60 for the left-sided LAM) and between A2 and A3 good to very good (0.76 right-sided/0.84 left-sided). CONCLUSIONS: Levator ani muscle trauma can reliably be diagnosed during all assessment periods. However, the agreement between A1 and A2 was only moderate to good. This can be explained by hematomas inside the LAM that were only observed early postpartum. We observed some anatomical improvement at A3, but no complete avulsion improved to an intact LAM.

Association between the side of levator Ani muscle trauma and fetal position at birth - a prospective observational study.

INTRODUCTION: Trauma of the levator ani muscle (LAM) is common after vaginal birth and can most reliably be diagnosed by 3-dimensional (3D) translabial ultrasound (TLUS). Multiple risk factors are known in general, but not in association to a specific side of the body. Therefore, our aim was to evaluate different impact factors which cause LAM trauma on either side of the body or bilateral by focusing on the fetal position at birth. MATERIAL AND METHODS: As part of a prospective cohort study between 3/2017 and 4/2019, we analyzed vaginal births of nulliparous women with singletons in vertex presentation≥36+0 gestational weeks. We evaluated their pelvic floor for hematomas, partial and complete LAM avulsions by 3D TLUS 2-4 days postpartum and searched for an association between the affected body side and different fetal, maternal and obstetrical factors. RESULTS: 71 out of 213 women (33.3%) suffered from LAM trauma - 17 (23.9%) on the right side, 20 (28.2%) on the left side and 34 (47.9%) bilateral. No association between the different evaluated factors and the affected body side could be identified, except for the quality of fetal heart rate tracing. CONCLUSIONS: No significant impact factors of LAM trauma could be associated with a specific side of the body. Other possible mechanisms need investigation in the future, such as the time of the birth canal and the fetus to adapt to each other, including adequate time for the tissue to stretch and the fetus to rotate into the ideal position within the LAM hiatus. EINLEITUNG: Levatormuskelverletzungen sind häufig nach Vaginalgeburten und können zuverlässig mittels translabialem 3D-Ultraschall diagnostiziert werden. Diverse Risikofaktoren sind hierfür bekannt, allerdings keine hinsichtlich der Assoziation zu einer der beiden Körperseiten. Daher war das Ziel dieser Arbeit, verschiedene Einflussfaktoren im Rahmen vaginaler Geburten zu evaluieren, welche eine Levatorverletzung auf einer der beiden Körperseiten bzw. beidseitig begünstigen, v. a. hinsichtlich der Kindsposition im Geburtskanal. MATERIAL UND METHODIK: In einer prospektiven Kohortenstudie analysierten wir von 3/2017-4/2019 Erstgebärende mit vaginalen Einlingsgeburten aus Schädellage≥36+0 SSW. Wir evaluierten 2-4 Tage postpartal ihren Beckenboden mittels 3D-Ultraschall hinsichtlich Hämatomen sowie partiellen und kompletten Levatoravulsionen und suchten nach Assoziationen zwischen der betroffenen Körperseite und fetalen, maternalen und geburtshilflichen Einflussfaktoren. ERGEBNISSE: Von 213 Frauen erlitten 71 (33.3%) eine Levatorverletzung - 17 (23.9%) rechtsseitig, 20 (28.2%) linksseitig und 34 (47.9%) beidseitig. Es wurden keine Assoziationen zwischen den untersuchten Einflussfaktoren und der betroffenen Körperseite gefunden, bis auf die Qualität der fetalen Herzfrequenz. DISKUSSION: Es konnten keine signifikanten Einflussfaktoren für das Auftreten einer Levatorverletzung einer spezifischen Körperseite eruiert werden. Daher bedarf es in Zukunft der Untersuchung weiterer Mechanismen, wie der Adaptationsvorgänge von Geburtskanal und Fet und der adäquaten Zeit für das Gewebe zur notwendigen Dehnung, v. a. im Bereich der Levatoröffnung.

[Placental Locations in Subsequent Pregnancies - A Retrospective Study]. / Plazentalokalisationen in aufeinanderfolgenden Schwangerschaften ­ eine retrospektive Kohortenstudie.

INTRODUCTION: Different locations of the placenta are associated with specific risks during pregnancy and labor. Knowledge of the placental location helps to provide better care for the expectant mother and her unborn child. Whereas multiple studies show a higher risk for a recurrent placenta previa, hardly any such data is available for any other placental location. The aim of this study was to analyze the frequency of distribution of different placental locations and to evaluate correlations between placental locations in subsequent pregnancies. MATERIAL AND METHODS: In a retrospective cohort study women with singleton pregnancies ≥ 24 gestational weeks who had at least one ultrasound with identification of the placental location and gave birth to their firstborn and at least one more following child at our hospital between 2007 and 2016 were evaluated. Exclusion criteria were multiple pregnancies, abortions, intrauterine fetal death, and fetal malformations. Placental locations were classified into anterior, posterior, fundal, right, left, and previa. RESULTS: Data of 1657 women were analyzed. The most frequent location was anterior, followed by posterior, fundal and lateral, and previa. Statistical analysis showed no significant correlations in subsequent pregnancies regarding placental locations. CONCLUSION: Placental locations in subsequent pregnancies seem not to be influenced by previous pregnancies. Therefore no prognosis for placental location can be made concerning future pregnancies.

Association between levator ani muscle avulsions and technique of vacuum extraction - a prospective exploratory study.

AIMS OF THE STUDY: Trauma of the levator ani muscle in the form of partial or complete avulsions is common after vaginal births, especially after vaginal-operative births. As there is little information available regarding associations between the technique of vaginal-operative births and levator ani muscle trauma, we aimed to evaluate the association between the process of vacuum extraction and the occurrence of levator ani muscle trauma. METHODS: As part of a prospective cohort study at the University Hospital of Zurich between March 2017 and April 2019, we sub-analysed vacuum extractions in nulliparous women with singletons in vertex presentation ≥36+0 gestational weeks. We evaluated their pelvic floor for partial and complete levator ani muscle avulsions using translabial ultrasound 6–10 weeks postpartum and calculated the association of the vacuum procedure itself, along with other fetal, maternal and obstetrical characteristics, with levator ani muscle trauma. RESULTS: Levator ani muscle trauma was present in 17 (34.7%) out of 49 women. There were no associations between the different factors evaluated and levator ani muscle trauma in vacuum-assisted births, except that the levator ani muscle group had insufficient uterine contractions. CONCLUSIONS: We found no fetal, maternal or obstetrical characteristics or parameters of vacuum technique that were associated with the occurrence of levator ani muscle trauma after vacuum extraction, except for insufficient uterine contractions. Nevertheless, there might be influencing factors that have not yet been evaluated, or are not easily accessible for evaluation, like the adaptations of the fetus inside the birth canal and within the hiatus of the levator ani muscle, and the adaptations of the birth canal to the fetus passing through. This should be the subject of further research with a sample size adequately powered to answer this question properly. (Trial registration number: BASEC-Nr.2016-00908.)  .

Birth tears after spontaneous and vacuum-assisted births with different vacuum cup systems - a retrospective cohort study.

Objectives Birth tears are a common complication of vaginal childbirth. We aimed to evaluate the outcomes of birth tears first by comparing the mode of vaginal birth (VB) and then comparing different vacuum cups in instrumental VBs in order to better advise childbearing women and obstetrical professionals. Methods In a retrospective cohort study, we analyzed nulliparous and multiparous women with a singleton pregnancy in vertex presentation at ≥37 + 0 gestational weeks who gave birth vaginally at our tertiary care center between 06/2012 and 12/2016. We compared the distribution of tear types in spontaneous births (SBs) vs. vacuum-assisted VBs. We then compared the tear distribution in the vacuum group when using the Kiwi Omnicup or Bird's anterior metal cup. Outcome parameters were the incidence and distribution of the different tear types dependent on the mode of delivery and type of vacuum cup. Results A total of 4549 SBs and 907 VBs were analyzed. Birth tear distribution differed significantly between the birth modes. In 15.2% of women with an SB an episiotomy was performed vs. 58.5% in women with a VB. Any kind of perineal tear was seen in 45.7% after SB and in 32.7% after VB. High-grade obstetric anal sphincter injuries (OASIS) appeared in 1.1% after SB and in 3.1% after VB. No significant changes in tear distribution were found between the two different VB modes. Conclusions There were more episiotomies, vaginal tears and OASIS after VB than after SB. In contrast, there were more low-grade perineal and labial tears after SB. No significant differences were found between different vacuum cup systems, just a slight trend toward different tear patterns.

Prediction of levator ani muscle avulsion by genital tears after vaginal birth-a prospective observational cohort study.

INTRODUCTION: Visible birth tears and levator ani muscle (LAM) trauma are common after birth. For the diagnosis of LAM trauma ultrasound evaluation is advisable. As ultrasound equipment and trained personnel are not available everywhere at all times, we aimed to evaluate whether specific overt birth tears are an indicator for LAM trauma. METHODS: In a prospective cohort study at our center from March 2017-April 2019, we evaluated vaginal births of nulliparous women with singletons in vertex presentation ≥ 36 + 0 gestational weeks for LAM trauma by translabial ultrasound and for overt birth tears by inspection. We then calculated the association of overt birth tears with complete LAM avulsion. RESULTS: Of 213 women, 23.9% had any kind of LAM trauma, with 14.1% being complete avulsions. In univariate analysis, solely high-grade perineal tears (OASIS) were significantly associated with complete LAM avulsions. CONCLUSIONS: Fourteen percent of women suffered a complete LAM avulsion after vaginal birth, with OASIS being the only associated parameter of significance. The occurrence of such trauma might be an indicator for a mismatch between the size of the fetus and the structures of the birth canal, leading to birth trauma. Assessing for LAM trauma by translabial ultrasound in women with OASIS might be worthwhile.

Birth Lacerations in Different Genital Compartments and their Effect on Maternal Subjective Outcome: A Prospective Observational Study.

INTRODUCTION: Lacerations are common in vaginal births, but little is known about tears other than perineal tears and their association with maternal impairment. This study aimed to evaluate the frequency and distribution of birth lacerations and their association with maternal discomfort. METHODS: From 2/2015 to 12/2016, we conducted a prospective observational study on 140 women with singletons in vertex presentation at term, who gave birth vaginally in our center and were affected by a laceration. The lacerations were assigned objectively and subjectively to eight genital tract compartments. The presence and effect of lacerations on maternal health were assessed by questionnaires for the time before birth (T1), 1-4 days (T2), and 6-8 weeks postpartum (T3). RESULTS: The number of affected compartments was 1.33 objectively and 2.99 at T2 and 1.27 at T3 subjectively. The most affected compartment was the right perineum (73%) followed by the right inner posterior (21%) and the right outer anterior (14%) compartment. Subjective and objective assessment concurred in 83% at T2 and 69% of cases at T3. Overall, impairment of women was low, reversible, and not directly associated with the location of lacerations, although women were psychologically affected. CONCLUSION: Birth lacerations predominantly appear at the right perineum. Physical impairment from these lacerations is generally low, reversible, and not directly associated with the location of lacerations, although psychological impairment is not negligible.

Maternal and neonatal outcome of reverse breech extraction of an impacted fetal head during caesarean section in advanced stage of labour: a retrospective cohort study.

BACKGROUND: Caesarean section with extraction of a deeply impacted fetal head is technically challenging and is associated with serious maternal and neonatal complications. The purpose of the study was to identify risks and evaluate selected outcome parameters associated with difficult fetal head extraction during caesarean section in advanced labour comparing two different extraction techniques (head pushing vs. reverse breech). METHODS: This retrospective cohort study was conducted at the Division of Obstetrics in a tertiary care hospital in Zurich, Switzerland. 629 women at term with a singleton pregnancy in cephalic presentation during advanced intrapartum caesarean section from December 2012 until December 2016 were evaluated. Primary outcome was the incidence of uterine incision extensions. Secondary outcomes were other selected maternal and neonatal outcome parameters. Data analysis was performed using SPSS with Mann-Whitney U independent sampling test and two-tailed Fisher's exact test (p < 0.01). RESULTS: Difficult fetal head extractions are associated with significantly elevated maternal and neonatal risks. When performed by reverse breech technique, significant lower rates of extensions of the uterine incision, shorter operation times and less operative blood loss were identified compared to the head pushing method. No statistically significant differences for the neonatal outcomes were described so far. However, among the group of difficult fetal delivery with the head pushing method two neonates had perinatal skull fractures, with one of those resulting in neonatal death. CONCLUSIONS: The head pushing method is associated with higher maternal morbidity than the reverse breech method for extraction of a deeply engaged fetus during intrapartum caesarean section in advanced stage of labour.

[Association of Birth Trauma with the Implementation of Obstetrical Monitoring Tools: A Retrospective Cohort Study]. / Assoziation zwischen Geburtsverletzungen und der Einführung geburtshilflicher Observationsmaßnahmen: eine retrospektive Kohortenstudie.

INTRODUCTION: Lacerations are common in vaginal births. They can result in immense physical and psychological morbidity. Ongoing efforts are being made to reduce birth trauma. We implemented different obstetrical monitoring tools in the labor ward and evaluated their association with the incidence and distribution of different types of birth lacerations. MATERIAL AND METHODS: We retrospectively analyzed nulliparous and multiparous women with singleton term pregnancies in vertex presentation, who gave birth vaginally in our tertiary care center between October 2014 and September 2015. We evaluated 3 different time intervals (T1=4 months before the implementation of the monitoring tools, T2=0-4 months and T3=5-8 months afterwards). Outcome parameters were the incidence and distribution of different types of birth lacerations during the 3 different time intervals. RESULTS: The incidence of all types of birth trauma decreased from 95,52% in nulliparous and 68,53% in multiparous women at T1 to 89,92% and 62,27% non-significantly at T3, with a decrease in perineal and vulvar/labial lacerations and an increase in vaginal lacerations. The rate of episiotomies and third-/fourth-degree perineal tears remained stable for nulliparous (33 and 3%) and multiparous (10 and 0.4%) women between the time intervals. CONCLUSION: The overall incidence of birth lacerations is high, with lacerations predominantly appearing as first- and second-degree perineal tears but also vaginal and labial lacerations. The initiation of different obstetrical monitoring tools is associated with a change in the incidence of birth traumas and a shift from an external to an internal distribution, probably due to more careful management by the obstetrical staff. The implementation of such tools might help to improve obstetrical management and laboring women might benefit. However, it is important to realize the effect of monitoring and observation itself on the course of observational studies.

Video analysis for the evaluation of vaginal births: a prospective observational study.

AIMS OF THE STUDY: Video documentation is nowadays well established in many fields of medicine, but mostly in unreal situations such as simulation training. We here present the application of video for teaching and learning purposes during the birth process. The aim of video documentation during labour is to provide an observational tool for obstetric care by midwives and obstetricians, with the opportunity for evaluation and education afterwards, especially in absence of the woman in labour and her family. METHODS: Between February 2015 and June 2017, we conducted a prospective observational study on women aged over 18 years with singleton pregnancies with vertex presentation at term, who gave birth vaginally in the labour ward at the Division of Obstetrics of the University Hospital of Zurich. The end of birth (crowning of the head and fetal extraction) with the manual actions and manoeuvers performed was recorded on video in 100 births. Procedures were analysed afterwards by a senior consultant and evaluated with the staff involved. RESULTS: We found frequent notable omissions during vaginal deliveries, concerning technical and nontechnical skills. Those aspects included inappropriate aseptic technique (e.g., no sterile underlay or sterile gloves), improper fetal head slowdown during expulsion, lack of visualisation of the perineum during fetal extraction/expulsion, lack of hip, shoulder and arm guiding while extracting the fetus, inappropriate episiotomy technique (wrong handling of the scissors, cutting angle too steep) and improper communication between the woman giving birth and the staff. During vacuum extractions, incorrect positioning of the cup, and inappropriate direction of pulling and handling of the cup were recorded. CONCLUSIONS: Video analysis of obstetric procedures in the labour ward is an easily applicable and very useful tool for teaching and learning purposes. It contributes to showing and improving the quality of procedures and the interactions of the staff and can be used for staff evaluation.

Impact factors on cervical dilation rates in the first stage of labor.

AIMS: To assess cervical dilation rates of nulliparous and multiparous women in the active first stage of labor and to evaluate significant impact factors. METHODS: In a retrospective cohort study between January 2007 and July 2014 at the University Hospital of Zurich in Switzerland, we analyzed 8378 women with singleton pregnancies in vertex presentation with a vaginal delivery at 34+0 to 42+5 gestational weeks. Median cervical dilation rates were calculated and different impact factors evaluated. RESULTS: Cervical dilation rates increase during labor progress with faster rates in multiparous compared with nulliparous women (P<0.001). Dilation rates exceed 1 cm/h at a dilatation of 6-7 cm, but are very individual. Accelerating impact factors are multiparity, a greater amount of cervical dilation and fetal occipitoanterior position, whereas the use of epidural anesthesia, a higher fetal weight and head circumference decelerate dilation (P<0.001). CONCLUSION: Cervical dilation is a hyperbolic increasing process, with faster dilation rates in multiparous compared to nulliparous women and a reversal point of labor around 6-7 cm, respectively. Besides, cervical dilation is highly individual and affected by several impact factors. The diagnosis of labor arrest or prolonged labor should therefore be based on such rates and on the individual evaluation of every woman.

[Diastasis Recti Abdominis and Pregnancy]. / Rektusdiastase und Schwangerschaft.

Diastasis recti abdominis during pregnancy is a frequent phenomenon with a prevalence of 30­70%. It is associated with functional and cosmetic limitations. Gold standard in diagnosis during pregnancy is the transabdominal ultrasonography. The most frequent localization is in the periumbilical region and persistence postpartum is found in about 60% of cases. Either conservative or surgical treatments seem to be effective, but relapse rates, especially after surgical therapy, are unclear. It is a problem that no standard values of diastasis recti are given, no evidence-based therapy schemes are implemented and only rare and insufficient studies exist.

A survey on Swiss women's preferred menstrual/withdrawal bleeding pattern over different phases of reproductive life and with use of hormonal contraception.

BACKGROUND: Today, options for bleeding-free lifestyle are actively promoted by the media, the pharmaceutical industry and health specialists. With regard to contraceptive counselling it is important to find out what women really want. METHODS: In the present study we collected information on women's attitudes towards monthly bleeding and preferences, if they could have the option to modify their individual bleeding pattern. Furthermore we evaluated the preferences with use of combined hormonal contraceptives (CHCs). Switzerland has never been surveyed before with regard to these issues. Questionnaires were distributed in our family planning clinic and two outdoor offices to clients aged 15 to 19 years, 25 to 34 years, and 45 to 49 years. RESULTS: Of 530 questionnaires, 292 were eligible for analysis. Around 50 of the participants would appreciate having fewer menstrual period-related symptoms. Some 37% preferred experiencing a monthly bleeding; 32% opted for every 2 to 6 months; and 29%, for no bleeding at all. This heterogeneous distribution did not differ between clients with and without menstrual symptoms. With regard to CHC use, predictable bleeding was rated as very positive and breakthrough bleeding as negative. CONCLUSION: Contraceptive counsellors should be aware that women's wishes differ widely. Predictability of bleeding seems to be more important to them than postponing it.

Maternal and neonatal outcome of labour induction at term comparing two regimens of misoprostol.

AIM: To compare the efficacy and safety of two misoprostol dosing regimens for induction of labour in primiparous (1P) and multiparous (>1P) women. METHODS: Retrospective study of induction of labour using vaginal misoprostol 25 µg vs. 50 µg every 6 h in 942 women at a tertiary centre. The main outcome variables are induction-to-delivery interval, latency period duration, vaginal delivery within 24 h, and maternal and foetal safety outcome. RESULTS: With the 50 µg regimen, induction-to-delivery intervals were significantly shorter: 18.4 h vs. 24.6 h (1P) and 14 h vs. 17.9 h (>1P), as was latency period duration (by 5.4 and 4 h, respectively). Vaginal delivery within 24 h was significantly more frequent, as were non-reassuring foetal heart rate (1P: 20% vs. 14%) and tachysystole (1P: 31% vs. 11%; >1P: 21% vs. 7%). No uterine rupture was reported. Neonatal outcomes were similar except for significantly more frequent infant referral to neonatal intensive care in the >1P group receiving the 50 µg regimen (11% vs. 4%). CONCLUSION: Vaginal misoprostol 25 µg seems to maintain efficacy with more acceptable maternal and neonatal safety. As induction of labour is an off-label use for misoprostol, safety should be prioritised with the lower dosage regimen despite the longer induction-to-delivery interval.

Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.