Anti-hypotensive treatment, which includes dopamine, dobutamine, epinephrine, norepinephrine, milrinone, vasopressin, terlipressin, levosimendan, and glucocorticoids, is a long-established intervention in neonates with arterial hypotension (AH). However, there are still gaps in knowledge and issues that need clarification. The main questions and challenges that neonatologists face relate to the reference ranges of arterial blood pressure in presumably healthy neonates in relation to gestational and postnatal age; the arterial blood pressure level that potentially affects perfusion of critical organs; the incorporation of targeted echocardiography and near-infrared spectroscopy for assessing heart function and cerebral perfusion in clinical practice; the indication, timing, and choice of medication for each individual patient; the limited randomized clinical trials in neonates with sometimes conflicting results; and the sparse data regarding the potential effect of early hypotension or anti-hypotensive medications on long-term neurodevelopment. In this review, after a short review of AH definitions used in neonates and existing data on pathophysiology of AH, we discuss currently available data on pharmacokinetic and hemodynamic effects, as well as the effectiveness and safety of anti-hypotensive medications in neonates. In addition, data on the comparisons between anti-hypotensive medications and current suggestions for the main indications of each medication are discussed.

Host defense against early-life infections such as chorioamnionitis, neonatal sepsis, or necrotizing enterocolitis (NEC) relies primarily on innate immunity, in which antimicrobial peptides (AMPs) play a major role. AMPs that are important for the fetus and neonate include α and β defensins, cathelicidin LL-37, antiproteases (elafin, SLPI), and hepcidin. They can be produced by the fetus or neonate, the placenta, chorioamniotic membranes, recruited neutrophils, and milk-protein ingestion or proteolysis. They possess antimicrobial, immunomodulating, inflammation-regulating, and tissue-repairing properties. AMPs are expressed as early as the 13th week and increase progressively through gestation. Limited studies are available on AMP expression and levels in the fetus and neonate. Nevertheless, existing evidence supports the role of AMPs in pathogenesis of chorioamnionitis, neonatal sepsis, and NEC, and their association with disease severity. This suggests a potential role of AMPs in diagnosis, prevention, prognosis, and treatment of sepsis and NEC. Herein, we present an overview of the antimicrobial and immunomodulating properties of human AMPs, their sources in the intrauterine environment, fetus, and neonate, and their changes during pre- and post-natal infections and NEC. We also discuss emerging data regarding the potential utility of AMPs in early-life infections, as diagnostic or predictive biomarkers and as therapeutic alternatives or adjuncts to antibiotic therapy considering the increase of antibiotic resistance in neonatal intensive care units.

Defining improvements in healthcare can be challenging due to the need to assess multiple outcomes and measures. In neonates, although progress in respiratory support has been a key factor in improving survival, the same degree of improvement has not been documented in certain outcomes, such as bronchopulmonary dysplasia. By exploring the evolution of neonatal respiratory care over the last 60 years, this review highlights not only the scientific advances that occurred with the application of invasive mechanical ventilation but also the weakness of the existing knowledge. The contributing role of non-invasive ventilation and less-invasive surfactant administration methods as well as of certain pharmacological therapies is also discussed. Moreover, we analyze the cost–benefit of neonatal care-respiratory support and present future challenges and perspectives.

Antibiotic, analgesic sedative, and antiseizure medications are among the most commonly used medications in preterm/sick neonates, who are at high risk of nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe and potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. The reported variability in the medications used in neonates indicates the lack of adequate neonatal studies regarding their effectiveness and safety. Important obstacles contributing to inadequate studies in preterm/sick infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the off-label use of many medications in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials (antifungals), analgesics (sedatives), and antiseizure medications in neonates, focusing on current evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage, and evidence-based guidelines for their optimal use in neonates. We also address the effects of early antibiotic use on the intestinal microbiome and its association with long-term immune-related diseases, obesity, and neurodevelopment (ND). Recommendations for empirical treatment and the emergence of pathogen resistance to antimicrobials and antifungals are also presented. Finally, future perspectives on the prevention, modification, or reversal of antibiotic resistance are discussed.

Objective The Downes score is a neonatal examination scoring tool frequently used to guide initiation of CPAP, but its ability to predict the need for surfactant has not been assessed. We assessed the extent to which the Downes score predicts the receipt of surfactant. Study design We calculated a simplified Downes score from nursing admission data for infants (≤ 2000 grams, and ≥ 25 weeks’ gestation) admitted on CPAP to a highly resourced level III NICU, to assess the predictive value for the receipt of surfactant. Results Fifty-three (31.5%) out of 168 infants admitted on CPAP received surfactant. A simplified Downes score of ≥ 4 predicted the receipt of surfactant with 90.6% sensitivity, 52.2% specificity, 46.6% positive predictive value, 92.3% negative predictive value, and 64.3% accuracy. Conclusion The high sensitivity and negative predictive value suggest utility for using the Downes score to help guide clinical decision making regarding surfactant therapy.

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO₂) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017–2024) was conducted in preterm infants < 32 weeks’ gestation who required >24 hours of invasive ventilation within the first 3 days of life. Perinatal-neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary-venous) and the maximum and minimum PCO₂ in the first 72 hours were evaluated. Normocapnia was defined as PCO₂ 35–45 mmHg, hypocapnia 45 mmHg. Primary outcomes were the incidence of PCO₂ abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age < 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age < 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO₂ values and greater PCO₂ variability, although these were not independent predictors of SBI or death. Conclusions: PCO₂ instability is highly prevalent in ventilated preterm infants necessitating personalized ventilation management. Extreme prematurity remains the strongest risk factor for adverse outcomes, while hypercapnia independently predicts BPD.