Hemodynamic Precision in the Neonatal Intensive Care Unit using Targeted Neonatal Echocardiography.

Targeted neonatal echocardiography (TnECHO) refers to the use of comprehensive echocardiographic evaluation and physiologic data to obtain accurate, reliable, and real-time information on developmental hemodynamics in sick newborns. The comprehensive assessment is based on a multiparametric approach that overcomes the reliability issues of individual measurements, allows for earlier recognition of cardiovascular compromise and promotes enhanced diagnostic precision and timely management. TnECHO-driven research has led to an enhanced understanding of the mechanisms of illness and the development of predictive models to identify at-risk populations. This information may then be used to formulate a diagnostic impression and provide individualized guidance for the selection of cardiovascular therapies. TnECHO is based on the expert consultative model in which a neonatologist, with advanced training in neonatal hemodynamics, performs comprehensive and standardized TnECHO assessments. The distinction from point of care ultrasonography (POCUS), which provides limited and brief one-time assessments, is important. Neonatal hemodynamics training is a 1-year structured program designed to optimize image acquisition, measurement analysis, and hemodynamic knowledge (physiology, pharmacotherapy) to support cardiovascular decision-making. Neonatologists with hemodynamic expertise are trained to recognize deviations from normal anatomy and appropriately refer cases of possible structural abnormalities. We provide an outline of neonatal hemodynamics training, the standardized TnECHO imaging protocol, and an example of representative echo findings in a hemodynamically significant patent ductus arteriosus.

Clinical Characteristics and Potential Pathogenesis of Cardiac Necrotizing Enterocolitis in Neonates with Congenital Heart Disease: A Narrative Review.

Neonates with congenital heart disease (CHD) are at an increased risk of developing necrotizing enterocolitis (NEC), an acute inflammatory intestinal injury most commonly associated with preterm infants. The rarity of this complex disease, termed cardiac NEC, has resulted in a dearth of information on its pathophysiology. However, a higher incidence in term infants, effects on more distal regions of the intestine, and potentially a differential immune response may distinguish cardiac NEC as a distinct condition from the more common preterm, classical NEC. In this review, risk factors, differentiated from those of classical NEC, are discussed according to their potential contribution to the disease process, and a general pathogenesis is postulated for cardiac NEC. Additionally, biomarkers specific to cardiac NEC, clinical outcomes, and strategies for achieving enteral feeds are discussed. Working towards an understanding of the mechanisms underlying cardiac NEC may aid in future diagnosis of the condition and provide potential therapeutic targets.

The Controversy Persists: Is There a Qualification Criterion to Utilize Inhaled Nitric Oxide in Pre-term Newborns?

Inhaled nitric oxide (iNO) use in premature newborns remains controversial among clinicians. In 2014, the American Academy of Pediatrics, Committee on Fetus and Newborn released a statement that the available data do not support routine iNO use in pre-term newborns. Despite the absence of significant benefits, 2016 California data showed that clinicians continue to utilize iNO in pre-term infants. With studies as recent as January 2017, the Cochrane review confirmed no major advantages of iNO in pre-term newborns. Still, it recognized that a subset of pre-term infants with pulmonary hypertension (PHTN) had not been separately investigated. Furthermore, recent non-randomized controlled trials have suggested that iNO may benefit specific subgroups of pre-term newborns, especially those with PHTN, prolonged rupture of membranes, and antenatal steroid exposure. Those pre-term infants who showed a clinical response to iNO had increased survival without disability. These findings underscore the need for future studies in pre-term newborns with hypoxemic respiratory failure and PHTN. This review will discuss the rationale for using iNO, controversies regarding the diagnosis of PHTN, and additional novel approaches of iNO treatment in perinatal asphyxia and neonatal resuscitation in the pre-term population < 34 weeks gestation.

Alterations in neonatal neutrophil function attributable to increased immature forms.

At birth neonatal neutrophil composition differs from that of adults due to a higher number of circulating immature forms. To date only a single study has evaluated neutrophil performance based on cell maturity. For this study, we examined functional differences in chemotaxis and phagocytosis between neonatal and adult neutrophils based on cell development and labor exposure. METHODS: Neutrophils were obtained by venipuncture from adults and cord blood from healthy term neonates delivered vaginally or by cesarean section. Transwells and the chemoattractant fMLP were used to evaluate chemotaxis. Phagocytosis assays were performed using GFP-labeled E.coli (RS218) and whole blood. Neutrophil maturation was measured by an accurate and verified flow cytometry technique using the markers CD45, CD11b, and CD16. QuantiGene Plex and Procarta immunoassays were used to determine cytokine and chemokine gene expression and protein concentration, respectively. RESULTS: Labor exposure did not alter neonatal neutrophil function in this study. Neonatal and adult mature neutrophils performed chemotaxis and phagocytosis equally well, while immature forms showed marked impairments. Neonatal immature granulocytes, though, completed chemotaxis more proficiently than those of adults. Although cytokine and chemokine levels varied between neonatal and adult groups, no differences were detected in neonates based upon labor exposure. CONCLUSION: Historically documented functional impairments of neonatal neutrophils may be due to the increased number of developmentally immature forms at birth rather than absolute global deficiencies.

Is the Use of Complete Blood Counts with Manual Differentials an Antiquated Method of Determining Neutrophil Composition in Newborns?

BACKGROUND: Automated complete blood counts (CBCs) provide imprecise measures of neonatal neutrophil composition due to the presence of nucleated red cells, which masquerade as white cells. Manual differentials (MDs) must be performed but can be flawed due to technician inexperience or limited cell counts. Our study evaluated whether flow cytometry could more accurately determine neutrophil composition in term newborns compared with adult controls. METHODS: Neutrophils were obtained by venipuncture in adults (n=10) and via cord blood from neonates delivered vaginally (n=21) or by primary cesarean section (n=17). Samples were processed by both flow cytometry and CBC with MD and results compared. Flow cytometry findings were verified using gene expression analysis of granule proteins. RESULTS: Immature-to-total neutrophil ratios were used to signify neutrophil composition. Flow cytometry was superior to manual differentials due to its ability to identify the earliest neutrophil forms. Significant differences between newborns and adults were determined using flow cytometry (0.12 versus 0.05; p=0.01), but not MDs (p=0.18). Neonates had similar findings irrespective of labor and method used. Verification of neutrophil maturity was completed using gene expression analysis of granule proteins. CONCLUSIONS: These results raise concerns about the accuracy of using CBCs with MDs to determine neutrophil composition. Further investigation of flow cytometry in clinical practice is warranted.

Fever.

PURPOSE OF REVIEW: The present review presents novel infections and better evidence on current practices related to fever in children. RECENT FINDINGS: Studies using more accurate diagnostic methods have provided evidence for prevalence of certain diseases, their clinical presentation and anticipated complications. Answers to certain clinical dilemmas related to febrile children in a pediatric office practice have been addressed recently. Some studies have explored current issues like immunization of pregnant women with influenza vaccine and the outbreak investigation of the swine H1N1 influenza. SUMMARY: Fever still remains the most common reason for visits to the pediatrician or emergency room. Better diagnostic methods; appropriate therapeutic or preventive strategies; and continued surveillance for novel infections have improved outcomes from both an individual and public health perspective.