Angiocrine IGFBP3 Spatially Coordinates IGF Signaling During Neonatal Cardiac Regeneration

To identify non cellautonomous effectors of cardiomyocyte mitosis, we analyzed a transcriptomic screen of regenerating and non regenerating neonatal hearts for differentially expressed secreted proteins, which we hypothesized could include candidate mitogens. We identified and validated IGFBP3, which has a Janus-like stabilizing and sequestering effect on IGF growth factors, as a neonatal injury associated secreted protein. IGFBP3 is expressed by and secreted from vascular cells in the neonatal heart after cardiac injury, notably in the infarct border zone. We found that global deletion of IGFBP3 blunted neonatal regeneration, while gain of function experiments using recombinant IGFBP3 and a transgenic mouse model uncovered a pro mitotic effect of IGFBP3 on cardiomyocytes in vitro and in the adult heart. We show that site specific expression of an IGFBP3 protease (PAPPA2) and its inhibitor (STC2) coordinate the spatial release of IGF2 in the infarct zone to regio selectively activate the INSR/ERK/AKT cell growth pathways in cardiomyocytes. Collectively, our work highlights the spatiotemporal orchestration of endothelial cardiomyocyte interactions that are required for neonatal cardiac regeneration.

Sudden severe fetal compromise at a planned home birth – a case of umbilical cord prolapse

Background Sudden severe fetal compromise during labor is usually associated with fetal bradycardia often due to sudden emergencies such as abruptio placentae, cord prolapse, disruption of the umbilical cord, shoulder dystocia, tetanic contractions or uterine rupture. Case presentation We report on a case of sudden severe fetal compromise due to umbilical cord prolapse in a patient with a planned home birth. Cord prolapse and thick meconium stained fluid were diagnosed at a planned home birth at the time of spontaneous rupture of fetal membranes with the cervix 3 cm dilated. An ambulance was called, and the patient was transferred by ambulance to the nearby hospital where the baby was delivered about 60 min after the diagnosis of the cord prolapse. Neonatal resuscitation was unsuccessful, and the newborn was declared dead. Conclusion Our case shows that sudden severe fetal compromise during labor and delivery can happen to even low-risk patients. When it happens at home, delay of delivery can lead to neonatal injury or death. Women who express an interest in a planned home birth must be informed of potential risks of sudden severe fetal compromise leading to neonatal injury or death when it occurs in a planned home birth and when transport to the hospital unavoidably delays timely medical interventions and delivery of the newborn.