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.
HighlightsThe HbbTh3/+ mouse is a good model of severe thalassemia for in utero therapy.In utero and postnatal transplantation with immunosuppression resulted in better chimerism.In utero gene therapy produced partial hematological correction but not full rescue.Both strategies need further optimization to overcome the hostile microenvironment.
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.
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