The role of neutrophil activation in determining the outcome of pregnancy and modulation by hormones and/or cytokines.

Neutrophils are often exclusively considered as a first-line innate immune defence, able to rapidly kill or trap pathogens and causing in case of over-activation tissue damage. In the female reproductive tract, however, the presence and activity of neutrophils seems to be tightly regulated. Major players in orchestrating this regulation are cyclical steroid sex hormones present during the menstrual cycle and pregnancy. This review describes the role of sex hormones in regulating directly or indirectly the functionality of neutrophils, the role of neutrophils during fertilization and pregnancy and in controlling viral, fungal and bacterial infection. This review also discusses the consequence of overt neutrophil activation in pregnancy pathologies.

Generalisability of randomised trials of the programmed intermittent epidural bolus technique for maintenance of labour analgesia: a prospective single centre cohort study.

BACKGROUND: Several randomised controlled trials show that maintenance of labour epidural analgesia with programmed intermittent epidural bolus reduces the maternal motor block compared with maintenance with a continuous infusion. However, these trials were usually restricted to healthy nulliparous parturients. To assess the generalisability of these randomised controlled trials to 'real-world' conditions, we compared maternal motor function (modified Bromage score) over time between healthy nulliparous and parous women using routinely collected quality-control data. METHODS: After ethical approval, all parturients receiving programmed intermittent epidural bolus labour analgesia between June 2013 and October 2014 were included in this prospective cohort study. Bupivacaine 0.1% with fentanyl 2 µg ml-1 was used allowing for patient-controlled bolus every 20 min. The maternal motor function (primary outcome) was regularly assessed from insertion of the epidural catheter until delivery. RESULTS: Of the 839 parturients included, 553 (66%) were nulliparous and 286 (34%) were parous. The parous women had a shorter median duration of epidural analgesia (3 h 59 min vs 5 h 45 min) and a higher incidence of spontaneous delivery (66% vs 37%). The probability of being in a certain Bromage category at birth was similar in nulliparous and parous women in a general additive model adjusting for duration of epidural analgesia, number of rescue top-ups, and number of catheter manipulations (cumulative odds ratio: 1.18; 95% confidence interval: 0.98-1.41). Parous women required a higher time-weighted number and volume of rescue top-ups. CONCLUSIONS: The results of the randomised controlled trials on a reduced motor block with programmed intermittent epidural bolus seem generalisable to parturients typically not included in these trials.

Efficacy and safety of carbetocin given as an intravenous bolus compared with short infusion for Caesarean section - double-blind, double-dummy, randomized controlled non-inferiority trial.

BACKGROUND: Carbetocin is a synthetic oxytocin-analogue, which should be administered as bolus according to manufacturer's recommendations. A higher speed of oxytocin administration leads to increased cardiovascular side-effects. It is unclear whether carbetocin administration as short infusion has the same efficacy on uterine tone compared with bolus administration and whether haemodynamic parameters differ. METHODS: In this randomized, double-blind, non-inferiority trial, women undergoing planned or unplanned Caesarean section (CS) under regional anaesthesia received a bolus and a short infusion, only one of which contained carbetocin 100 mcg (double dummy). Obstetricians quantified uterine tone two, three, five and 10 min after cord-clamping by manual palpation using a linear analogue scale from 0 to 100. We evaluated whether the lower limit of the 95% CI of the difference in maximum uterine tone within the first five min after cord-clamping did not include the pre-specified non-inferiority limit of -10. RESULTS: Between December 2014 and November 2015, 69 patients were randomized to receive carbetocin as bolus and 71 to receive it as short infusion. Maximal uterine tone was 89 in the bolus and 88 in the short infusion group (mean difference -1.3, 95% CI -5.7 to 3.1). Bp, calculated blood loss, use of additional uterotonics, and side-effects were comparable. CONCLUSIONS: Administration of carbetocin as short infusion does not compromise uterine tone and has similar cardiovascular side-effects as a slow i.v. bolus. In accordance with current recommendations for oxytocin, carbetocin can safely be administered as short -infusion during planned or unplanned CS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02221531 and www.kofam.ch SNCTP000001197.

Decreased neonatal pain response after vaginal-operative delivery with Kiwi OmniCup versus metal ventouse.

BACKGROUND: Vaginal delivery, especially operative assisted vaginal delivery, seems to be a major stressor for the neonate. The objective of this study was to evaluate the stress response after metal cup versus Kiwi Omnicup® ventouse delivery. METHODS: The study was a secondary observational analysis of data from a former prospective randomised placebo controlled multicentre study on the analgesic effect of acetaminophen in neonates after operative vaginal delivery and took place at three Swiss tertiary hospitals. Healthy pregnant women ≥35 weeks of gestation with an estimated fetal birth weight above 2000 g were recruited after admission to the labour ward. Pain reaction was analysed by pain expression score EDIN scale (Échelle Douleur Inconfort Nouveau-Né, neonatal pain and discomfort scale) directly after delivery. For measurement of the biochemical stress response, salivary cortisol as well as the Bernese Pain Scale of Newborns (BPSN) were evaluated before and after an acute pain stimulus (the standard heel prick for metabolic testing (Guthrie test)) at 48-72 h. RESULTS: Infants born by vaginal operative delivery displayed a lower pain response after plastic cup than metal cup ventouse delivery (p < 0.001), but the pain response was generally lower than expected and they recovered fully within 72 h. CONCLUSIONS: Neonatal pain response is slightly reduced after use of Kiwi OmniCup® versus metal cup ventouse. TRIAL REGISTRATION: Trial was registered under under NCT00488540 on 19th June 2007.

Postnatal retention in HIV care: insight from the Swiss HIV Cohort Study over a 15-year observational period.

OBJECTIVES: The aim of this study was to quantify loss to follow-up (LTFU) in HIV care after delivery and to identify risk factors for LTFU, and implications for HIV disease progression and subsequent pregnancies. METHODS: We used data on pregnancies within the Swiss HIV Cohort Study from 1996 to 2011. A delayed clinical visit was defined as > 180 days and LTFU as no visit for > 365 days after delivery. Logistic regression analysis was used to identify risk factors for LTFU. RESULTS: A total of 695 pregnancies in 580 women were included in the study, of which 115 (17%) were subsequent pregnancies. Median maternal age was 32 years (IQR 28-36 years) and 104 (15%) women reported any history of injecting drug use (IDU). Overall, 233 of 695 (34%) women had a delayed visit in the year after delivery and 84 (12%) women were lost to follow-up. Being lost to follow-up was significantly associated with a history of IDU [adjusted odds ratio (aOR) 2.79; 95% confidence interval (CI) 1.32-5.88; P = 0.007] and not achieving an undetectable HIV viral load (VL) at delivery (aOR 2.42; 95% CI 1.21-4.85; P = 0.017) after adjusting for maternal age, ethnicity and being on antiretroviral therapy (ART) at conception. Forty-three of 84 (55%) women returned to care after LTFU. Half of them (20 of 41) with available CD4 had a CD4 count < 350 cells/µL and 15% (six of 41) a CD4 count < 200 cells/µL at their return. CONCLUSIONS: A history of IDU and detectable HIV VL at delivery were associated with LTFU. Effective strategies are warranted to retain women in care beyond pregnancy and to avoid CD4 cell count decline. ART continuation should be advised especially if a subsequent pregnancy is planned.

Pregnancy and Infants' Outcome: Nutritional and Metabolic Implications.

Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.

[Periodontal diseases--a review on the association between maternal periodontitis and adverse pregnancy outcome]. / Parodontale Erkrankungen--Eine Übersicht über die Beziehung mütterlicher Parodontitis und negativer Schwangerschaftsergebnisse.

Several prospective clinical trials have indicated an association between maternal periodontal status and adverse pregnancy outcome, e.g., low birth weight, pre-term birth and pre-eclampsia. However, the translation of these findings into clinical care and decision making is still a matter of debate. Gynecologists and obstetricians are usually not very familiar with periodontal diseases and do not always consider this pathology in routine preconception counselling. This article outlines the clinical pictures of the most common periodontal diseases and thus helps the gynecologists to identify patients with periodontal diseases.

Amniotic fluid embolism: A comparison of two classification systems in a retrospective 8-year analysis from two tertiary hospitals.

OBJECTIVE: Amniotic fluid embolism (AFE) is a rare life-threatening complication in obstetrics, but the diagnosis lacks a consensual definition. The objective of this study was to compare two different AFE classification systems by analysing the AFE cases from two university hospitals. MATERIAL AND METHODS: In this retrospective study, all patients with a strong suspicion of AFE between 2014 and 2021 at two university hospitals, LMU Women's University Hospital Munich, and Women's University Hospital Basel, were included. Patient records were checked for the ICD-10 code O88.1 (AFE). Diagnoses were confirmed through clinical findings and/or autopsy. The presence of the diagnostic criteria of the Society of Maternal foetal Medicine (SMFM) and the AFE Foundation (AFEF) and of a new framework by Ponzio-Klijanienko et al. from Paris, France, were checked and compared using Chi-square-test. RESULTS: Within our study period, 38,934 women delivered in the two hospitals. Six patients had a strong suspicion of AFE (0.015%). Only three of six patients (50%) presented with all the four diagnostic criteria of the SMFM/AFEF framework. All six patients met the criteria of the modified "Paris AFE framework". CONCLUSION: Using the "Paris AFE framework" based exclusively on clinical criteria can help clinicians to diagnose AFE, anticipate the life-threatening condition of the patient and prepare immediately for best clinical care.

Oral misoprostol vs. intravenous oxytocin in reducing blood loss after emergency cesarean delivery.

OBJECTIVE: To compare the effectiveness of oral misoprostol and intravenous oxytocin in reducing blood loss in women undergoing indicated or elective cesarean delivery (CD) under spinal anesthesia. METHODS: In this prospective, double-blind pilot study, 56 parturients who received 5 IU of intravenous oxytocin after cord clamping were randomized to further receive either misoprostol orally and a placebo infusion intravenously or placebo orally and an oxytocin infusion intravenously. RESULTS: After adjustment was made for the sonographically estimated amniotic fluid volume, there was no statistical difference in blood loss between the 2 groups (mean+/-S.D., 1083+/-920 mL in the oxytocin group vs. 970+/-560 mL in the misoprostol group; P=.59). CONCLUSION: Oxytocin followed by oral misoprostol is as effective as an oxytocin injection followed by an oxytocin infusion in reducing postoperative blood loss after CD, and the protocol may be a safe, valuable, and cost-effective alternative to oxytocin alone. Visual estimation of intraoperative blood loss undervalues the effective value of misoprostol use by 30%.

Screening of gestational diabetes mellitus in early pregnancy by oral glucose tolerance test and glycosylated fibronectin: study protocol for an international, prospective, multicentre cohort trial.

INTRODUCTION: As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an 'early' oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort. METHODS AND ANALYSIS: In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an 'early' OGTT 75 g and/or the new biomarker, glyFn, at 12-15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24-28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on 'early' OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014. ETHICS AND DISSEMINATION: This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered under http://www.ClinicalTrials.gov (NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02035059.

Spontaneous fetal loss rates in a non-selected population.

The objective of this work was to determine the rate of spontaneous fetal loss up to 28 weeks of gestation in uncomplicated pregnancies of a low-risk population after sonographically identified intact intrauterine pregnancy during the first trimester. Transvaginal ultrasounds were given to 2,534 women at between six and 12 weeks of gestation. Inclusion criteria were a positive fetal cardiac activity and no antecedent signs of vaginal bleeding. Gestational age was confirmed by measurement of the crown-rump length and/or biparietal diameter (BIP). Patients were followed until delivery or up to a fetal loss. The mean fetal loss rate between 12 and 28 weeks was 3.86% (n = 99). Fetal loss increased with maternal age: fetal loss rate under 20 yr: 2.94% (OR 0.75; CI 0.23-2. 46), 20-24 yr: 3.20% (OR 0.77; CI 0.48-1.23), 25-29 yr: 3.39% (OR 0.77; CI 0.50-1.19), 30-34 yr: 3.89% (OR 1.01; CI 0.59-1.71), 35-39 yr: 7.82% (OR 2.13; CI 1.04-4.32), 40-45 y: 50% (OR 13.84; CI 6.67-28.72) and > 45 yr: 50% (OR 13.05; CI 1.96-86.71) respectively. The frequency of spontaneous fetal loss before 28 weeks gestation was assessed systematically in a low-risk population. There was a very clear correlation with advancing maternal age. These data now can be used as background loss rate information for evaluating the safety of invasive prenatal diagnosis, and they will be more valid for this purpose than the available data taken from selected cohorts of women, such as those from hospital clinics or from infertility programs.

Three dimensional volume measurement of the cervix during pregnancy compared to conventional 2D-sonography.

OBJECTIVE: To compare the three dimensional (3D) volume assessment of the cervix with the conventional two-dimensional cervical length measurement in a low and a high risk group for cervical incompetence. METHODS: In an observational study, we investigated a group A of low risk pregnancies (no preterm contractions, no vaginal bleeding or vaginal infections and no history of preterm delivery) and a group B of high risk pregnancies (preterm contractions or PROM). All patients underwent a transvaginal ultrasound investigation with a 7.5 MHz probe using a three-dimensional ultrasound system (Combison 530, Kretztechnik, Austria). After measuring the cervical length, the internal os and the funneling with the B-mode, 3D-volume was recorded twice by the same investigator using the same machine. Since 2D-length measurement of the cervix has been established to be predictive for spontaneous preterm delivery, we wanted to test whether 3D-volume assessment has a better discriminative power to differentiate a high-risk from a low-risk group. Therefore the 2D and 3D measurements (mm, resp. cm3) were compared between patient groups A and B using the two tailed Student t-test and Fisher's Exact test. RESULTS: In 2D cervical length measurement the mean cervical length in group A was significantly longer than in group B: 41.1 +/- 8.61 mm and 27.77 +/- 10.42 mm, P = 0.00000017. In 3D-sonography the mean cervical volume was larger in group A, but the difference compared to group B was not significant: 47.71 +/- 18.38 mm and 39.90 +/- 12.57 mm, P = 0.07. CONCLUSION: Contrary to our hypothesis cervical length measurement therefore was superior to cervical volume measurement assessed by 3D ultrasound for identifying women with increased risk of spontaneous preterm delivery. This may be due to the larger distribution of measurement values in the 3D group.

Charts for cervical length in singleton pregnancy.

OBJECTIVES: To construct charts for cervical length in a low risk population measured by transvaginal ultrasonography. METHODS: Pregnant women of an apparently normal population were seen in the ultrasound division of the University Women's Hospital Basel between 20 and 34 weeks of gestation and underwent once (one measurement per subject) a transvaginal ultrasound measurement of the cervix under standardized conditions. In order to establish normal values of the cervical length, finally only women who delivered spontaneously at term (>37 weeks of gestation) remained in the study. Exclusion criteria were preterm labor, multiple pregnancies, cerclage or surgical intervention prior to pregnancy. For statistical evaluation, regression analysis and calculation of 5th and 95th percentiles were performed. RESULTS: A total of 669 cervical measurements were recorded. The number of measurements differed from 22 measurements at 23 weeks of gestation to 86 at 31 weeks of gestation. Cervical length gradually and significantly decreased as the gestational age progressed (between 20 and 34 weeks of gestation). New charts with the 5th, 50th and 95th percentile are presented and compared with previously published data. CONCLUSIONS: Our charts for cervical length in a limited risk population can be used for observing patients at high risk of preterm delivery and for clearly identifying a significant deviation or decline in the percentile for these subjects.

Medical and obstetric problems complicating pregnancy.

The present review addresses several medical and obstetric factors/problems, and their interactions during pregnancy. These include the following: maternal age; morbidity and mortality during pregnancy; thromboembolism; gestational diabetes; haemolysis, elevated liver enzymes, low platelets syndrome; human immunodeficiency virus; hepatitis C; preterm labour; antenatal administration of corticosteroids; intrapartum surveillance; breech delivery; and caesarean section.

Morphology assessed by transvaginal ultrasonography differs in patients in preterm labor with vs. without bacterial vaginosis.

OBJECTIVE: To determine whether cervical morphology in preterm labor patients differs in the presence or absence of bacterial vaginosis. DESIGN: Observational study. SUBJECTS: One hundred and twelve consecutive patients with objectively confirmed preterm labor admitted to a tertiary care centre were included in the study. Patients with placenta previa, active uterine bleeding or indication for an immediate delivery (e.g. severe pre-eclampsia or suspected fetal asphyxia), or severe fetal anomalies were excluded. METHODS: Transvaginal ultrasonography was used to measure cervical length and internal os width. Bacterial vaginosis was diagnosed by Gram stain of a vaginal smear. RESULTS: A total of 36 patients (32%) had bacterial vaginosis. Cervical length in this group was shorter than in patients with normal flora (mean 20.4 +/- 7.2 mm vs. 26.4 +/- 6.7 mm; P = 0.0002), and more patients with bacterial vaginosis had a dilated internal cervical os > or = 5 mm (67% vs. 30%, P = 0.001). There were no significant differences, however, in preterm delivery rate and birth weight between the two groups; the overall preterm delivery rate was 40%. A cervical length < 25 mm was predictive of preterm delivery (P = 0.001, RR 4.2, 95% CI 1.8-9.7). CONCLUSIONS: These data suggest that cervical change in preterm labor is more pronounced in patients with bacterial vaginosis but without a concomitant increase in the risk for preterm delivery. Despite this association, the cervical length measured by transvaginal ultrasonography alone is a useful predictor of preterm delivery, independent of the presence or absence of bacterial vaginosis.

Differentiation and management of endometrium abnormalities and leiomyomas by hydrosonography.

Transvaginal sonography is an established method for numerous clinical indications in the assessment of endometrium pathology. The investigation of the endometrium consists of the measurement of the thickness, the visualization of the echogenity and echotexture and of the demonstration of focal masses. However, evaluation of the uterine cavity by transvaginal sonography is limited and an abnormal ultrasound of the endometrium may reflect benign or malignant conditions. Furthermore, small structures can be missed or overlooked. If indicated, hydrosonography offers various advantages compared to dilatation and curettage and hysteroscopy in terms of costs, availability and risks. Additional informations obtained after hydrosonography may influence the management before consideration of curettage or hysteroscopy.

Virilizing ovarian tumor of low malignant potential associated with antecedent tamoxifen use for breast cancer.

A patient is described who was treated with tamoxifen for breast cancer and developed an androgen-producing ovarian tumor of low malignant potential, which itself is a rare condition. Clinically overt virilism was leading to the diagnosis and promptly improved after surgical removal of the tumor. A causal relationship between tamoxifen use and the tumor is discussed on the basis of the known tumor-inducing potential of tamoxifen.

A double-blind comparison of the safety and efficacy of intravaginal misoprostol and prostaglandin E2 to induce labor.

OBJECTIVE: Our purpose was to compare the safety and efficacy of intravaginally administered misoprostol versus prostaglandin E2 for labor induction in a double-blind, randomized trial. STUDY DESIGN: One hundred three patients with indications for labor induction (including prelabor rupture of membranes) were randomized and received either misoprostol 50 micrograms or prostaglandin E2 (dinoprostone) 3 mg intravaginally. The dose was repeated 6, 24, and 30 hours after the first dose until active labor was achieved. For proper blinding, the drugs were prepared as identical-looking vaginal tablets. RESULTS: With use of a random number-generated table 52 patients were allocated to the misoprostol group and 51 to the prostaglandin E2 group. After exclusion of 3 patients, 50 in each group were evaluated. Delivery within 24 hours after administration occurred more often in the misoprostol group (70% vs 46% in the prostaglandin E2 group, p = 0.009), and fewer patients in this group needed more than two doses (12% vs 30%, p = 0.027). No difference in cesarean section rate (12% vs 14%, p = 0.67), fetal heart rate anomalies (33% vs 34%, p = 0.89), tachysystole (8% vs 14%, p = 0.37), hyperstimulation syndrome (0% vs 2%, not significant), meconium passage (28% vs 18%, p = 0.22), and fetal outcome (Apgar score at 1 and 5 minutes, arterial and venous umbilical cord blood pH, transfer to neonatal intensive care unit) was noted between the two groups. CONCLUSION: Intravaginal misoprostol is a safe drug for labor induction with superior effectiveness compared with intravaginal prostaglandin E2.