Effects of female genital mutilation on birth outcomes in Switzerland.

OBJECTIVE: The primary aim of this study was to determine the desires and wishes of pregnant patients vis-à-vis their external genital anatomy after female genital mutilation (FGM) in the context of antenatal care and delivery in a teaching hospital setting in Switzerland. Our secondary aim was to determine whether women with FGM and non-mutilated women have different fetal and maternal outcomes. DESIGN: A retrospective case-control study. SETTING: A teaching hospital. POPULATION: One hundred and twenty-two patients after FGM who gave consent to participate in this study and who delivered in the Department of Obstetrics and Gynaecology in the University Hospital of Berne and 110 controls. METHODS: Data for patients' wishes concerning their FGM management, their satisfaction with the postpartum outcome and intrapartum and postpartum maternal and fetal data. As a control group, we used a group of pregnant women without FGM who delivered at the same time and who were matched for maternal age. MAIN OUTCOME MEASURES: Patients' satisfaction after delivery and defibulation after FGM, maternal and fetal delivery data and postpartum outcome measures. RESULTS: Six percent of patients wished to have their FGM defibulated antenatally, 43% requested a defibulation during labour, 34% desired a defibulation during labour only if considered necessary by the medical staff and 17% were unable to express their expectations. There were no differences for FGM patients and controls regarding fetal outcome, maternal blood loss or duration of delivery. FGM patients had significantly more often an emergency Caesarean section and third-degree vaginal tears, and significantly less first-degree and second-degree tears. CONCLUSION: An interdisciplinary approach may support optimal antenatal and intrapartum management and also the prevention of FGM in newborn daughters.

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%.

[Stem cells from cord blood: current status and future potential]. / Stammzellen aus Nabelschnurblut: Aktuelle Bedeutung und zukünftiges Potenzial.

Umbilical cord blood is rich in hematopoietic stem cells. At birth, it can be collected, HLA-typed and stored. Cord blood is successfully used since over 10 years as source of transplantation of hematopoietic stem cells, in addition to bone marrow and mobilized peripheral blood stem cells. Allogeneic transplantations are performed between HLA-identical siblings and from HLA-matched unrelated donors. Most recipients of cord blood are children with Leukemia or genetic disorders, but also increasingly adolescents and adults. Based on the promising results, cord blood banks with kryopreserved, HLA-typed cord blood samples from anonymous donors are set up worldwide, ready to be used as allogeneic stem cell graft. In addition, so-called "private" cord blood banks have been set up, providing the possibility to store cord blood at birth from healthy children with no affected family member for a possible autologous stem cell transplantation in the future if the child later develops a disease such as Leukemia. For several reasons, however, this procedure has been scientifically as well as ethically challenged. To date, there is no established indication for an autologous cord blood transplantation. Nevertheless, the plasticity and multipotency of adult stem cells, which has been recently discovered, could lead to a possible autologous use of cord blood stem cells for different indications in the field of regenerative medicine (cell- and organ replacement/regeneration). So far, however, this remains speculatative. Research in the field of stem cell development and differentiation in the next decade will try to find some answers.

[Prenatal stem cell transplantation: from bench to bedside]. / Vorgeburtliche Stammzelltransplantation zwischen Forschung und Klinik.

Prenatal stem cell transplantation is a novel, promising therapeutic option for genetic disorders, which is now at the edge of moving from preclinical research into clinical application. The first clinical experience shows that inborn diseases, which lead to a severe immunodeficiency, can be treated successfully inutero. No therapeutic success has been achieved in genetic disorders which do not severely affect the immune system. Therefore, new strategies to improve the success are being developed, including e.g., graft modification, prenatal conditioning of the fetus, postnatal re-transplantation after prenatal induction of immune tolerance, and fetal gene therapy using autologous fetal stem cells. The use of non-hematopoietic (e.g. mesenchymal) or pluripotent stem cells will most probably lead to an expansion of the spectrum of indications in genetic diseases for this novel treatment. At the same time, however, ethical implications, in particular regarding fetal gene therapy and the use of pluripotent stem cells must be evaluated.

[Current aspects of labor induction]. / Aktuelle Aspekte der Geburtseinleitung.

Induction of labor is one of the most important means for therapeutic intervention in modern obstetrics. The aim of labor induction is to achieve a better perinatal result for mother and baby as compared to expectative management. Different methods for induction include administration of oxytocin or prostaglandins, amniotomy, and mechanical means of cervical dilatation. The success of the labor induction depends primarily on the readiness of the uterus to go into labor, and the method used for induction. If the cervical ripeness is very advanced, induction with amniotomy and oxytocin seems beneficial. However if the cervix is not yet ready, intravaginal or intracervical prostaglandins are more promising. Until recently, prostaglandins E2 are used in the first line. Now, the prostaglandin E1-analogon misoprostol is also increasingly used. As a rule, induction of labor should be performed as an inpatient procedure in order to be able to provide the surveillance for maternal and fetal safety.

Effect of preeclampsia on umbilical cord blood hematopoietic progenitor-stem cells.

OBJECTIVE: The aim of the present study was to determine the influence of preeclampsia on cord blood hematopoietic progenitor-stem cells obtained at delivery because cord blood is increasingly used clinically for stem cell retrieval as an alternative to bone marrow. STUDY DESIGN: Umbilical cord blood was collected from patients fulfilling the criteria for preeclampsia and from gestational age- and birth weight-matched control subjects at delivery (patient/control subjects ratio, 1:2). Cord blood volume and nucleated cell content were measured, and the number of hematopoietic progenitor-stem cells was determined by means of fluorescence-activated cell sorting with the CD34(+) epitope and by means of colony assays with different hematopoietic growth factors. In addition, the expression of adhesion molecules by CD34(+) progenitor-stem cells was examined. RESULTS: In pregnancies affected by preeclampsia, volume and nucleated cell and total CD34(+) cell contents in the collected cord blood were significantly smaller compared with those of control subjects. Furthermore, there was a trend toward a smaller relative number of CD34(+) cells and colony-forming units per nucleated cell in cord blood samples from preeclamptic patients. No difference in the expression of the cell-adhesion molecules leukocyte function-associated antigen 1, very late activation antigen 4, and L-selectin by CD34(+) cells could be found. CONCLUSION: This study shows that preeclampsia affects umbilical cord blood volume and nucleated cell and progenitor-stem cell numbers obtained at birth.

Fetal cells from cord blood as stem cell source: current status and possible implications in gynaecologic oncology.

Umbilical cord blood is increasingly used as a source of hematopoietic stem cells for transplantation. Due to recent success, cord blood banks are being set up. We reviewed the currently available literature concerning cord blood collection, storage and transplantation, the impact of prenatal and perinatal factors and collection techniques on the quantity and quality of cord blood, and the ethical, legal and social questions related to cord blood transplantation. Possible implications in gynecologic oncology are reviewed and discussed. The emerging therapeutic use of cord blood for transplantation and transfusion implies new challenges for the speciality of gynecology and obstetrics.

Fanconi anemia associated with increased nuchal translucency detected by first-trimester ultrasound.

Increased nuchal translucency between 10 and 14 weeks of gestation has now been established as a marker for chromosomal defects in several large-scale studies. In addition, a growing number of structural defects and some rare genetic syndromes have been identified in association with this marker. We describe a case of a fetus with increased nuchal translucency at 12 weeks of gestation, in which second-trimester evaluation by ultrasound showed an enlarged cisterna magna, a ventricular septal defect and moderate signs of dysmorphia. Karyotyping by chorionic villus sampling revealed a high rate of chromosomal breaks. The diagnosis of Fanconi anemia with early onset was confirmed following the development of severe postnatal anemia 2 months after birth.

Haematopoietic stem cell transplantation and gene therapy in the fetus: ready for clinical use?

Allogeneic haematopoietic stem cell transplantation in utero has been successfully used for the prenatal treatment of severe combined immunodefiency syndrome. However, this treatment has not been successful in the therapy of other conditions in which the fetus is immunologically competent. The main obstacles to success are lack of competitive advantage of donor versus host stem cells, preventing stable engraftment and graft rejection. Several strategies are being explored to overcome these problems, and some of them have been successful in animal studies. Prenatal gene therapy, using ex-vivo transduced autologous haematopoietic cells or direct gene targeting in utero, is another potential approach in the treatment of immunocompetent fetal recipients. Although this has been shown to be feasible in animal models, safety concerns regarding transduction of fetal germ cells or maternal cells should be addressed in preclinical experiments prior to initiation of clinical trials.

Developmental changes in adhesion molecule expressions in umbilical cord blood CD34 hematopoietic progenitor and stem cells.

OBJECTIVE: The purpose of this study was to determine whether expressions of the cell adhesion molecules LFA-1 (CD11a), VLA-4 (CD49d), and L -selectin (CD62L ) on CD34(+) stem and progenitor cells in umbilical cord blood change during gestation. STUDY DESIGN: In a prospective observational study 3-color fluorescence-activated cell sorting was used to assess the levels of expression of CD11a, CD49d, and CD62L on CD34(+) cells in fresh cord blood samples collected at delivery between 22 and 42 weeks' gestation. RESULTS: The relative number of CD34(+) cells decreased as gestational age increased (r = -0.71; P<.001). Conversely, we found significant increases in cell adhesion molecule expression by CD34(+) cells during gestation (LFA-1, r = 0.47; P =.001; VLA-4, r = 0.33, P =.031; L -selectin, r = 0.61; P<.001). Comparisons between grouped samples from early preterm (22-32 weeks' gestation), late preterm (33-37 weeks' gestation), and term (38-42 weeks' gestation) infants confirmed this correlation and revealed that the major increases occurred between early and late preterm gestation. CONCLUSION: These results suggest a role for cell adhesion molecule expression in the process of migration and homing of circulating stem cells to the fetal bone marrow toward the end of pregnancy. The findings may have implications for the use of preterm cord blood for hematopoietic stem cell transplantation and also for prenatal gene therapy.

Preterm birth and the availability of cord blood for HPC transplantation.

BACKGROUND: Cord blood from deliveries at term can be used for HPC transplantation. The objective of this study was to determine the amounts of cord blood nucleated cells (NCs) and HPCs that were collectable from preterm deliveries. STUDY DESIGN AND METHODS: Cord blood collected from preterm deliveries between 22 and 36 weeks of gestation was compared with regard to volume, NC count (/mL), CD34+ cell count (/mL), and the NC and CD34+ cell counts per cord blood sample and at different gestational ages. RESULTS: A correlation was found between gestational age and NC count (r = 0.52, p<0.001), and an inverse relation was found between gestational age and CD34+ cell count (r = - 0.68, p<0.001). The CD34+ cell count per cord blood sample was independent of gestational age (r = - 0.13, p = NS), and no significant difference between early (22-32 week) and late (33-36 week) preterm deliveries was found (p = 0.870). Comparison with published data from cord blood transplantations revealed that up to one-third of preterm samples contained at least as many NCs (or CD34+ cells) as the median cell dose transplanted (calculated for the median recipient weight) in the respective study. Furthermore, 77 percent of all preterm samples contained at least 1 x 10(7) NCs (and 42% at least 1 x 10(5) CD34+ cells) per kg for transplantation in a recipient of 20-kg body weight, which corresponds to the lower threshold of cells per kg in the graft recommended by Eurocord. CONCLUSION: Preterm delivery should not be a reason to exclude cord blood collection if allogeneic cord blood transplantation in a sibling is planned.

Umbilical cord blood collection before placental delivery during cesarean delivery increases cord blood volume and nucleated cell number available for transplantation.

OBJECTIVE: We sought to determine whether umbilical cord blood collection during cesarean delivery can be improved by collecting cord blood before delivery of the placenta. STUDY DESIGN: Patients undergoing cesarean delivery were randomly assigned to cord blood collection before or after placental delivery. Closed sterile collection systems were used for blood sampling. Cord blood characteristics and maternal outcome parameters were compared between the 2 groups. RESULTS: A total number of 40 patients were available for analysis. No differences in maternal and neonatal characteristics were found. A larger amount of cord blood volume (mean +/- SEM, 93 +/- 7.5 vs 66 +/- 6.6 mL; P =.013) and total nucleated cell number (11.1 +/- 1.2 vs 7.4 +/- 0.8 x 10(8) cells; P =.026) was obtained in the samples collected before compared with those collected after placental delivery. Similarly, there was a trend toward higher total CD34(+) cell number in samples collected in situ (30.0 +/- 6.0 vs 17.4 +/- 2.4 x 10(5) cells; P =.076). Estimated intraoperative blood loss, difference between prepartum and postpartum hemoglobin values, operating time, and puerperal infection rates were similar in both groups. CONCLUSION: If a cesarean delivery is performed, cord blood sampling is more efficacious if performed before delivery of the placenta. This collection method seems beneficial and safe and might therefore be preferably used for related, as well as unrelated, cord blood stem cell banking and transplantation.

Transabdominal first trimester embryofetoscopy as a potential approach to early in utero stem cell transplantation and gene therapy.

OBJECTIVE: To explore the potential of embryofetoscopy for early diagnosis and for access to the fetal circulation in the first trimester of gestation. DESIGN: Transabdominal embryofetoscopy was performed in 14 patients scheduled for termination of pregnancy using a 1-mm semirigid fibreoptic telescope with a 18 gauge examination sheath and a single-chip digital camera. A 25 gauge needle was inserted through an additional 21 gauge side port to access the fetal circulation. RESULTS: Fetal head, face, abdomen, complete upper and lower limbs could be visualized in over 80% of cases. On the contrary, the fetal back and external genitalia could be examined in detail only in some cases (35.7% and 64.3%, respectively). Injection of 10-20 ml saline improved visibility in 43% of cases. Funipuncture was successful in two of three attempts. CONCLUSIONS: Our experience suggests that embryofetoscopy is a useful tool for early diagnosis in the first trimester of pregnancy. Funipuncture is possible thus providing the means for an early intravascular stem cell application.

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.