Reducing primary cesarean delivery rate through implementation of a smart intrapartum surveillance system.

The rapid changes in clinical maternity situations that occur in a labor and delivery unit can lead to unpredictable maternal and newborn morbidities. Cesarean section (CS) rate is a key indicator of the accessibility and quality of a labor and delivery unit. This retrospective cross-sectional study assesses the nulliparous, term, singleton, vertex (NTSV) cesarean delivery rates before and after the implementation of a smart intrapartum surveillance system. Research data were collected from the electronic medical records of a labor and delivery unit. The primary outcome was the CS rate of the NTSV population. The data of 3648 women admitted for delivery were analyzed. Of the studied deliveries, 1760 and 1888 occurred during the preimplementation and postimplementation periods, respectively. The CS rate for the NTSV population was 31.0% and 23.3% during the preimplementation and postimplementation periods, respectively, indicating a significant 24.7% (p = 0.014) reduction in CS rate after the implementation of the smart intrapartum surveillance system (relative risk, 0.75; 95% confidence interval, 0.71-0.80). In the NTSV population, the vaginal and CS birth groups, no significant difference in terms of newborn weight, neonatal Apgar scores, composite neonatal adverse outcome indicator, and the occurrence of the following: neonatal intensive care unit admission, neonatal meconium aspiration, chorioamnionitis, shoulder dystocia, perineal laceration, placental abruption, postpartum hemorrhage, maternal blood transfusion, and hysterectomy before and after the implementation of the smart intrapartum surveillance system. This study reveals that the use of the smart intrapartum surveillance system can effectively reduce the primary CS rate for low-risk NTSV pregnancies without significantly affecting perinatal outcomes.

A comparison of intrauterine hemopoietic cell transplantation and lentiviral gene transfer for the correction of severe ß-thalassemia in a HbbTh3/+ murine model.

Major hemoglobinopathies place tremendous strain on global resources. Intrauterine hemopoietic cell transplantation (IUHCT) and gene transfer (IUGT) can potentially reduce perinatal morbidities with greater efficacy than postnatal therapy alone. We performed both procedures in the thalassemic HbbTh3/+ mouse. Intraperitoneal delivery of co-isogenic cells at embryonic days13-14 produced dose-dependent chimerism. High-dose adult bone marrow (BM) cells maintained 0.2-3.1% chimerism over ~24 weeks and treated heterozygotes (HET) demonstrated higher chimerism than wild-type (WT) pups (1.6% vs. 0.7%). Fetalliver (FL) cells produced higher chimerism than BM when transplanted at thesame doses, maintaining 1.8-2.4% chimerism over ~32 weeks. We boosted transplanted mice postnatally with BM cells after busulfan conditioning. Engraftment was maintained at >1% only in chimeras. IUHCT-treated nonchimeras and non-IUHCT mice showed microchimerism or no chimerism. Improved engraftment was observed with a higher initial chimerism, in HET mice and with the addition of fludarabine. Chimeric HET mice expressed 2.2-15.1% engraftment with eventual decline at 24 weeks (vs. <1% in nonchimeras) and demonstrated improved hematological indices and smaller spleens compared with untreated HETmice. Intravenous delivery of GLOBE lentiviral-vector expressing human ß-globin (HBB) resulted in a vector concentration of 0.001-0.6 copies/cell. Most hematological indices were higher in treated than untreated HET mice, including hemoglobin and mean corpuscular volume, but were still lower than in WT. Therefore, direct IUGT and IUHCT strategies can be used to achieve hematological improvement but require further dose optimization. IUHCT will be useful combined with postnatal transplantation to further enhance engraftment.

In utero therapy for congenital disorders using amniotic fluid stem cells.

Congenital diseases are responsible for over a third of all pediatric hospital admissions. Advances in prenatal screening and molecular diagnosis have allowed the detection of many life-threatening genetic diseases early in gestation. In utero transplantation (IUT) with stem cells could cure affected fetuses but so far in humans, successful IUT using allogeneic hematopoietic stem cells (HSCs), has been limited to fetuses with severe immunologic defects and more recently IUT with allogeneic mesenchymal stem cell transplantation, has improved phenotype in osteogenesis imperfecta. The options of preemptive treatment of congenital diseases in utero by stem cell or gene therapy changes the perspective of congenital diseases since it may avoid the need for postnatal treatment and reduce future costs. Amniotic fluid stem (AFS) cells have been isolated and characterized in human, mice, rodents, rabbit, and sheep and are a potential source of cells for therapeutic applications in disorders for treatment prenatally or postnatally. Gene transfer to the cells with long-term transgenic protein expression is feasible. Recently, pre-clinical autologous transplantation of transduced cells has been achieved in fetal sheep using minimally invasive ultrasound guided injection techniques. Clinically relevant levels of transgenic protein were expressed in the blood of transplanted lambs for at least 6 months. The cells have also demonstrated the potential of repair in a range of pre-clinical disease models such as neurological disorders, tracheal repair, bladder injury, and diaphragmatic hernia repair in neonates or adults. These results have been encouraging, and bring personalized tissue engineering for prenatal treatment of genetic disorders closer to the clinic.