Seminars in Perinatology

No abstract text is available yet for this article.

No abstract text is available yet for this article.

There is confusion regarding the dynamics of the umbilical cord circulation and the concomitant placental transfusion. How long does it continue, and at what rate? These questions remain an enigma for many. In this article we will address some common misconceptions about the management of cord circulation, try to explain why there is a lack of clarity, and call in to question the conclusions from an influential meta-analysis and a recently published guideline on cord clamping. We will do that partly by reviewing the rather extensive literature published on the subject over the past 50 to 70 years, which is easily forgotten, but worth considering...

Congenital diaphragmatic hernia (CDH) is a severe birth anomaly where a defect in the diaphragm allows abdominal organs to herniate into the chest with compression of the intrathoracic structures, specifically the lungs and heart. Pulmonary and left ventricular hypoplasia result in respiratory insufficiency after birth with disordered transition and persistent pulmonary hypertension of the newborn (PPHN). As a result, infants need immediate intervention after birth to support the transition. Delayed cord clamping (DCC) is recommended for all healthy newborns and improves outcomes in infants born preterm and in infants with congenital heart disease; however, DCC may not be feasible in newborns needing immediate intervention after birth...

Over the last 20 years, stem cells of varying origin and their associated secretome have been investigated as a therapeutic option for a myriad of neonatal models of disease, with very promising results. Despite the devastating nature of some of these disorders, translation of the preclinical evidence to the bedside has been slow. In this review, we explore the existing clinical evidence for stem cell therapies in neonates, highlight the barriers faced by researchers and suggest potential solutions to move the field forward...

Transamniotic stem cell therapy (TRASCET) is an emerging strategy for prenatal stem cell therapy involving the least invasive method described to date of delivering select stem cells to virtually any anatomical site in the fetus, including the blood and bone marrow, as well as to fetal annexes, including the placenta. Such broad therapeutic potential derives, to a large extent, from unique routing patterns following stem cell delivery into the amniotic fluid, which have commonalities with naturally occurring fetal cell kinetics...

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Preterm birth and intrapartum related complications account for a substantial amount of mortality and morbidity in the neonatal period despite significant advancements in neonatal-perinatal care. Currently, there is a noticeable lack of curative or preventative therapies available for any of the most common complications of prematurity including bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia and retinopathy of prematurity or hypoxic-ischemic encephalopathy, the main cause of perinatal brain injury in term infants...

Lung diseases are a main cause of mortality and morbidity in neonates. Despite major breakthroughs, therapies remain supportive and, in some instances, contribute to lung injury. Because the neonatal lung is still developing, the ideal therapy should be capable of preventing/repairing lung injury while at the same time, promoting lung growth. Cell-based therapies hold high hopes based on laboratory experiments in animal models of neonatal lung injury. Mesenchymal stromal cells and amnion epithelial cells are now in early phase clinical trials to test the feasibility, safety and early signs of efficacy in preterm infants at risk of developing bronchopulmonary dysplasia...

Stem cell research and the use of stem cells in therapy have seen tremendous growth in the last two decades. Neonatal intestinal disorders such as necrotizing enterocolitis, Hirschsprung disease, and gastroschisis have high morbidity and mortality and limited treatment options with varying success rates. Stem cells have been used in several pre-clinical studies to address various neonatal disorders with promising results. Stem cell and patient population selection, timing of therapy, as well as safety and quality control are some of the challenges that must be addressed prior to the widespread clinical application of stem cells...

During fetal life, the ductus arteriosus (DA) acquires the mechanisms for its postnatal closure following a thorough developmental program. This program can be interrupted by preterm birth and is also susceptible to alteration during fetal life by numerous physiological and pathological stimuli. In this review, we aim to summarize the evidence on how physiological and pathological factors affect DA development, eventually leading to patent DA (PDA). Specifically, we reviewed the associations of sex, race, and pathophysiological pathways leading to very preterm birth (endotypes) with PDA incidence and pharmacological closure...

The hemodynamically significant patent ductus arteriosus (hsPDA) is a controversial topic in neonatology, particularly among neonates at the earliest gestational ages of 22+0 -23+6  weeks. There is little, to no data on the natural history or impact of the PDA in extremely preterm babies. In addition, these high-risk patients have typically been excluded from randomized clinical trials of PDA treatment. In this work, we present the impact of early hemodynamic screening (HS) of a cohort of patients born 22+0 -23+6 weeks gestation who either were diagnosed with hsPDA or died in the first postnatal week as compared to a historical control (HC) cohort...

While cyclooxygenase inhibitors have been the most common medications used to facilitate earlier closure of patent ductus arteriosus in preterm infants, adverse effects and low efficacy in extremely low gestational age neonates (ELGANs) have highlighted a need for alternative options. Combination therapy with acetaminophen and ibuprofen is a novel strategy for PDA treatment in ELGANs, as it may facilitate higher ductal closure rates via additive action on two separate pathways inhibiting prostaglandin production...

The ductus arteriosus (DA) connects the aorta to the pulmonary artery (PA), directing placentally oxygenated blood away from the developing lungs. High pulmonary vascular resistance and low systemic vascular resistance facilitate shunting of blood in utero from the pulmonary to the systemic circulation through the widely patent DA, thereby optimizing fetal oxygen (O2 ) delivery. With the transition from fetal (hypoxia) to neonatal (normoxia) oxygen conditions, the DA constricts while the PA dilates. This process often fails in prematurity, promoting congenital heart disease...

Platelet plug formation is critically involved in murine ductus arteriosus closure and thrombocytopenia in preterm infants seems to negatively affect spontaneous and pharmacologically induced ductal closure. Furthermore, platelet dysfunction may contribute to ductal patency, especially in extremely immature infants. Neonatal platelets likely have multifaceted roles during ductal closure, such as secretion of several signaling molecules and facilitation of specific cell-cell interactions. The only available randomized-controlled trial on platelet transfusions in preterm infants with patent ductus arteriosus demonstrated that a liberal transfusion regimen did not promote ductal closure, but was associated with an increased rate of intraventricular hemorrhage...

Progressive remodeling throughout the fetal and postnatal period is essential for anatomical closure of the ductus arteriosus (DA). Internal elastic lamina interruption and subendothelial region widening, elastic fiber formation impairment in the tunica media, and intimal thickening are distinctive features of the fetal DA. After birth, the DA undergoes further extracellular matrix-mediated remodeling. Based on the knowledge obtained from mouse models and human disease, recent studies revealed a molecular mechanism of DA remodeling...

A persistent left-to-right shunt through a patent ductus arteriosus (PDA) increases the rate of pulmonary hydrostatic fluid filtration, impairs pulmonary mechanics, and prolongs the need for respiratory support. Infants with a moderate/large PDA shunt that persists for more than 7-14 days are at increased risk for developing bronchopulmonary dysplasia (BPD) if they also require invasive ventilation for more than 10 days. In contrast, infants who require invasive ventilation for less than 10 days have similar rates of BPD no matter how long they are exposed to a moderate/large PDA shunt...

No abstract text is available yet for this article.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease that primarily affects premature infants. Necrotizing enterocolitis is associated with adverse two-year outcomes, yet limited research has evaluated the impact of NEC on long-term complications and quality of life in children older than two years. We conducted a survey to characterize the long-term impact of NEC on physical and mental health, social experiences, and quality of life as self-reported by adult NEC survivors and parents of children who survived NEC...

In this review, we provide a historical perspective on probiotic use in preterm infants. We review recent data on the treatment effects of probiotics on necrotizing enterocolitis, sepsis, and mortality. We highlight guidance statements from professional societies and organizations, discussing key points within the context of the currently available evidence from both randomized trials and cohort studies. Finally, we summarize experiences from several North American centers that have reported on the routine use of probiotics, including our center...