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.

Pulmonary hypertension (PH) is a serious and potentially life-threatening condition in neonates, often resulting from impaired transition from fetal to postnatal circulation. Although traditionally associated with elevated pulmonary vascular resistance and hypoxemic respiratory failure, PH in infants who are preterm encompasses a spectrum of pathophysiologic mechanisms and can be broadly categorized into 3 phenotypes: precapillary, postcapillary, and flow driven. Each phenotype presents with distinct hemodynamic features and clinical implications. Although pulmonary vasodilators such as inhaled nitric oxide remain a cornerstone of therapy for PH, their efficacy and safety vary significantly depending on the underlying phenotype and etiology. In this narrative review, we examine the evolving understanding of PH in infants who are premature and propose a physiologically grounded framework for diagnosis, phenotyping, and individualized management.

Mechanical ventilation remains a cornerstone of neonatal intensive care, particularly for premature infants with respiratory distress syndrome. While blood gas analysis and radiographs provide clinical information, ventilator pulmonary graphics offer continuous, noninvasive insights into respiratory mechanics. Modern ventilators generate real-time data that help clinicians assess lung compliance, airway resistance, and patient-ventilator synchrony. Pressure-volume and flow-volume loops provide visual cues for detecting changes in compliance, air leaks, secretions, overdistension, air trapping, and autocycling. Understanding these graphical patterns supports individualized ventilator adjustments and early recognition of evolving pulmonary pathology. In this review, we provide clinicians in the neonatal intensive care unit with a toolbox to help analyze ventilator graphics in mechanically ventilated infants.

Preterm infants face significant growth challenges due to high metabolic demands, limited nutrient reserves, poor temperature control, and prolonged illness. These challenges are prevalent in all neonatal intensive care units, irrespective of the level of resources available. In low- and middle-income countries (LMICs), preterm infant nutrition risk can be exacerbated by constrained tangible and human resources, making the provision of adequate nutrition even more difficult. In this article, we explore neonatal growth and nutrition in LMICs and identify key strategies that clinicians can adopt to optimize the use of available enteral and parenteral nutrition resources. We address the following approaches: (1) when and how to use alternative fortifiers if infant formula is cost-prohibitive, (2) strategies to optimize intravenous fluids in the absence of total parenteral nutrition, (3) nonfeeding interventions to optimize growth, and (4) discharge feeding strategies and ongoing growth assessments for extremely low-birth-weight infants. The findings of this article highlight the importance of tailored nutritional approaches, the need for innovative resource management, and the critical role of interdisciplinary collaboration in enhancing the care of preterm infants globally.

Congenital long QT syndrome (LQTS) is a cardiac channelopathy caused by mutations in cardiac ion channel genes, leading to delayed ventricular repolarization, QT interval prolongation, and risk of malignant arrhythmias and sudden cardiac death. The condition often presents during childhood or adolescence but can be identified in neonates, particularly when there is a positive family history. Early recognition is critical, as timely intervention with beta-blockers and avoidance of QT-prolonging medications can prevent life-threatening events. We report the case of a full-term neonate born via cesarean section to a mother with congenital long QT syndrome (LQT2) and a strong family history of arrhythmic events. On day 1 of life, screening electrocardiogram (ECG) revealed a markedly prolonged corrected QT (QTc) prompting neonatal intensive care unit admission for further monitoring and evaluation. Propranolol was initiated, resulting in gradual QTc improvement over the first week of life. Genetic testing confirmed LQT2, with a pathogenic KCNH2 variant identified. The infant remained clinically stable and asymptomatic throughout hospitalization. The diagnosis of LQTS relies on a combination of ECG findings, clinical history, and genetic testing. Beta-blockers are the first-line therapy, and avoiding QT-prolonging medications is critical. In neonates, early recognition and treatment are vital to prevent arrhythmias. This case highlights the importance of early neonatal ECG screening in the setting of a family history of LQTS and emphasizes the need for multidisciplinary approach to optimize diagnosis, treatment, and counseling.

Uncertainty exists within many aspects of neonatal care. However, neonatal intensive care unit clinicians report varying comfort levels with managing uncertainty in clinical care. Although accepting ambiguity and demonstrating proficiency in communication are required components of medical education, there is a lack of formal curricula on uncertainty in medicine. Despite this, clinicians must find ways to effectively partner with parents to develop care plans in situations with elements of uncertainty. This article reviews frameworks of uncertainty, perspectives, and experiences of parents and neonatologists; examines approaches to navigating uncertainty in clinical care; and suggests the need for formal training to manage uncertainty in neonatology.