Small molecule therapies that restore function to the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein, referred to as CFTR modulators, have emerged as a key therapeutic approach for people with CF who carry responsive genetic variants. Their effects have been transformative to the lives of many of those living with CF. As the reach of CFTR modulators expands, new questions arise about their role beyond approved clinical indications for people with CF. One such area of growing interest is the use of CFTR modulator therapy during pregnancy to treat suspected meconium ileus, a particularly severe fetal and immediate postnatal manifestation of CF. In this review, we summarize the current data about use of CFTR modulator therapy during pregnancy, including reported effects in pregnant persons and their offspring. We describe the potential of this in utero therapy to prevent meconium ileus and to maintain exocrine pancreatic function in infants with CF. However, these potential benefits must be weighed carefully with the known and potential risks of CFTR modulator therapy. We address ethical implications and important knowledge gaps related to prenatal CFTR modulator use during pregnancy. Further evidence is needed to determine best practices for CFTR modulator use during pregnancy.

In the early 1960s, the newborn screening (NBS) program in the United States began with testing for phenylketonuria. Since that time, the NBS program has greatly expanded the number of disorders tested in all newborns. This article reviews the importance of NBS from a public health perspective as well as in the clinical setting to detect, diagnose, and manage conditions early. Current practices vary across the United States as well as internationally. While there have been several advancements in NBS over the past several decades, multiple challenges and limitations remain. Some of these challenges include false-positive and false-negative results, the ethical dilemma of consent, and optimal timing of NBS in the neonatal intensive care unit. Future directions of NBS, both nationally and internationally, include the implementation of next-generation sequencing testing and artificial intelligence.

Severe combined immunodeficiency (SCID) is a rare and life-threatening disease, characterized by an intrinsic defect of the hematopoietic stem cell that disrupts appropriate T lymphocyte maturation. Previously, early diagnosis of SCID used to require an experienced physician who identified patients with abnormal absolute lymphocyte count and distinct clinical manifestations. Over the past few decades, the implementation of universal newborn screening has enhanced our diagnostic capabilities. The Pediatric Immune Deficiency Treatment Consortium updated the definitions of SCID in 2022, providing a comprehensive approach to differentiate patients with typical SCID from leaky or atypical SCID, and Omenn syndrome from those without SCID. SCID is caused by multiple genetic abnormalities with different phenotypes involving T cells and possibly natural killer cells, and B cells. The management of patients with SCID requires a multifocal approach with early interventions to prevent infections and the concurrent planning of a curative therapy such as hematopoietic stem cell transplantation or, in some cases, gene therapy. Early intervention in affected patients with the absence of infection is a predictor of good long-term outcomes, but because of evolving bone marrow transplant and gene therapy techniques, patients need to be monitored long term to assess for possible late side effects. This review will focus on the most common genetic causes of SCID and their distinct characteristics, acute management, and curative options.

Neonatal cerebral hemodynamics represents a complex process affected by dynamic circulatory changes. Understanding the pathophysiology and factors that may affect cerebral blood flow in neonates is crucial to addressing the circulatory mechanism for neonatal brain injury. Studies have described multiple tools for monitoring cerebral blood flow; however, these are limited by the impracticality of using invasive tools. In this review, we explain the physiology of neonatal cerebral autoregulation with a focus on the transitional period and summarize the currently available methods for monitoring.

Umbilical cord blood (UCB) has garnered attention as a potentially valuable resource in neonatal medicine. Blood from the cord contains a rich population of stem and progenitor cells, including hematopoietic stem cells, mesenchymal stromal cells, and endothelial progenitor cells, each offering unique therapeutic potential. Early clinical studies and preclinical trials have suggested that these cells may be able to promote tissue repair, provide neuroprotection, and modulate the immune system, potentially providing promising therapeutic avenues for neonates with limited treatment options. Current research has focused on the safety, feasibility, and preliminary efficacy of UCB-based therapies, particularly in neonates with brain injuries, lung diseases, and hematological disorders. Despite positive early results, the field is still evolving, and large-scale clinical trials are underway to further evaluate the potential of UCB-derived cells in neonates. In this review, we examine the diverse roles of UCB-derived cells in potentially treating neonatal diseases such as anemia, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and bronchopulmonary dysplasia. We also discuss future directions for the application of UCB-derived cells in transfusion and regenerative medicine.