Dexmedetomidine is a promising sedative and analgesic for newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Pharmacokinetics and safety of dexmedetomidine were evaluated in a phase I, single-center, open-label study to inform future trial strategies. We recruited 7 neonates ≥36 weeks’ gestational age diagnosed with moderate-to-severe HIE, who received a continuous dexmedetomidine infusion during TH and the 6 h rewarming period. Time course of plasma dexmedetomidine concentration was characterized by serial blood sampling during and after the 64.8 ± 6.9 hours of infusion. Noncompartmental analysis yielded descriptive pharmacokinetic estimates: plasma clearance of 0.760 ± 0.155 L/h/kg, steady-state distribution volume of 5.22 ± 2.62 L/kg, and mean residence time of 6.84 ± 3.20 h. Naive pooled and population analyses according to a one-compartment model provided similar estimates of clearance and distribution volume. Overall, clearance was either comparable or lower, distribution volume was larger, and mean residence time or elimination half-life was longer in cooled newborns with HIE compared to corresponding estimates previously reported for uncooled (normothermic) newborns without HIE at comparable gestational and postmenstrual ages. As a result, plasma concentrations in cooled newborns with HIE rose more slowly in the initial hours of infusion compared to predicted concentration-time profiles based on reported pharmacokinetic parameters in normothermic newborns without HIE, while similar steady-state levels were achieved. No acute adverse events were associated with dexmedetomidine treatment. While dexmedetomidine appeared safe for neonates with HIE during TH at infusion doses up to 0.4 μg/kg/h, a loading dose strategy may be needed to overcome the initial lag in rise of plasma dexmedetomidine concentration.
This review summarizes high-quality evidence supporting delayed umbilical cord clamping to promote placental transfusion to preterm and term neonates. In preterm neonates, delayed cord clamping may decrease mortality and the need for blood transfusions. Although robust data are lacking to guide cord management strategies in many clinical scenarios, emerging literature is reviewed on numerous topics including delivery mode, twin gestations, maternal comorbidities (eg, gestational diabetes, red blood cell alloimmunization, human immunodeficiency virus [HIV] infection, and severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and neonatal complications (eg, fetal growth restriction, congenital heart disease, and the depressed neonate). Umbilical cord milking is an alternate method of rapid placental transfusion, but has been associated with severe intraventricular hemorrhage in extremely preterm neonates. Data on long-term outcomes are discussed, as well as potential contraindications to delayed cord clamping. Overall, delayed cord clamping offers potential benefits to the estimated 140 million neonates born globally every year, emphasizing the importance of this simple and no-cost strategy.
Premature neonates hospitalized in the neonatal intensive care unit (NICU) have high nutritional needs to ensure optimal growth and development. Monitoring adherence to neonatal nutritional guidelines and providing personalized nutritional recommendations are essential for promoting their health. However, ensuring consistent adherence to these guidelines is challenging. To address this, we developed a clinical decision support system using an ontology and rule-based approach to offer personalized nutrition recommendations for preterm infants in the NICU. The Nutrition Recommendation Ontology (NRO) was developed, incorporating 121 classes, 366 axioms, and 157 semantic rules based on standard nutrition guidelines and retrospective data from 601 NICU patients, using a cumulative 8460 patient-days data collected from a single center between 2019-2021. While the ontology represented the conceptual knowledge, the rules encoded the procedural knowledge. The integrated NRO-based system serves as a reasoning engine, enabling the generation of patient-specific feeding recommendations and assisting in identifying deviations from established guidelines. To validate its efficacy, the NRO system was tested on 10 sample case studies and achieved 98% accuracy, as assessed by a panel of neonatologists. Our findings indicate that the NRO-based clinical decision support system can provide accurate personalized nutrition recommendations and assess guideline adherence in the NICU. With further real-world validation, we anticipate that this approach could significantly improve nutrition delivery, prevent malnutrition, and ultimately improve outcomes for preterm infants.