Current Pediatric Reviews - Volume 19, Issue 4, 2023

Neonatal anaemia is a very frequent clinical condition that may be due to apparent or not evident blood loss, decreased red blood cells (RBCs) production, or increased destruction of RBCs. RBCs transfusion criteria are clearly defined by several national and locally agreed guidelines. However, it is not possible to define a unique cut-off to guide clinicians' transfusion practice, which needs a multiparametric analysis of demographic variables (gestational age, postnatal age, birth weight), clinical evaluation, conventional and new generation monitoring (such as echocardiography and near-infrared spectroscopy). Unfortunately, few tools are available in the delivery room to help neonatologists in the management of newborn with acute anaemia. Early volume replacement with cristalloids and RBCs transfusion could be life-saving in the delivery room when a hypovolaemic shock is suspected, but the use of un-crossmatched whole is not risk-free nor easily available in clinical practice. Placental transfusion could be an extremely effective and inexpensive method to increase haemoglobin (Hb), to improve oxygen delivery, and to increase cardiac output with a reduced need for RBCs transfusions, a reduced risk of intraventricular haemorrhages, and an improved survival of the newborn.

The use of FFP in neonatology should be primarily for neonates with active bleeding and associated coagulopathy. However, since there is limited and poor-quality evidence supporting neonatal FFP transfusion, considerable FFP usage continues to be outside of this recommendation, as documented by neonatal transfusion audits. This review updates the scientific evidence available on FFP use in neonatology and reports the best evidence-practice for the safety of neonates receiving FFP.

Background: The non-specific and antigen-specific components of host defense mechanisms are subject to the adaptation process in the neonate; however, the neutrophil quantitative and qualitative deficiency is one of the most significant causative factors of neonatal-increased vulnerability to infection. Objective: To review the incidence and outcome of neutropenia of unknown cause in preterm infants. Results: The incidence of early and late-onset idiopathic neutropenia of prematurity is significant. Conclusion: The low neutrophil counts respond quickly to G-CSF treatment; however, due to the low probability of septic complications, particularly in the late-onset neutropenia, a deep diagnostic approach and the potential hematopoietic growth factor treatment should be limited to the severe cases, such as a neutrophil count <500/μL, lasting for more than 2 days.

The assessment of hemostasis and the prediction of bleeding risk are of great importance to neonatologists. Premature infants are at an increased risk for bleeding, particularly intra-cranial hemorrhages (most commonly intra-ventricular hemorrhages (IVH)), gastrointestinal hemorrhages, and pulmonary hemorrhages. All severe bleeding, but especially severe IVH, is associated with poor neurodevelopmental outcomes, and other than prenatal steroids, no intervention has reduced the incidence of this serious complication. As a result, there is a need in neonatology to more accurately identify at-risk infants as well as effective interventions to prevent severe bleeding. Unfortunately, the commonly available tests to evaluate the hemostatic system were established using adult physiologic principles and did not consider the neonate's different but developmentally appropriate hemostatic system. This review will describe the changes in the platelet count and tests of hemostasis throughout development, the limitations of these tests to predict neonatal bleeding and the utility of treating abnormal results from these tests with platelet and/or fresh frozen plasma (FFP) transfusions in non-bleeding infants.

Severe thrombosis in the neonate presents a diagnostic challenge to the clinician as the benefits and risks for treatment must be weighed with every medical decision. Aortic thromboses, large right atrial thromboses, and septic thrombophlebitis present unique clinical challenges that must be managed in the appropriate clinical setting with appropriate subspecialty support. Unfortunately, there is limited data on what the ideal therapy should be for these specific types of cases. In this review, we will discuss these types of severe thromboses that may occur in neonates and potential therapies that may offer benefits.

Historically blood for admission laboratory studies in neonates was obtained through direct neonatal phlebotomy. Over the past decade, there has been a significant increase in studies evaluating the validity and clinical impact of using a cord blood sample for many admission laboratory studies. This article reviews various studies that together suggest that using cord blood samples for admission testing in neonates is both acceptable and beneficial.

Hemolytic disorders can cause severe morbidity or can be life-threatening. Before the recent development of practical and inexpensive testing for hemolysis by quantifying carbon monoxide in end-tidal breath, some hemolytic disorders in perinatal patients were not detected until severely problematic hyperbilirubinemia and/or anemia occurred. Here we review studies aimed at establishing the normal reference intervals for end tidal breath carbon monoxide (ETCO) in various perinatal populations. We also review reports, and new theories, about using this methodology to diagnose and quantify hemolytic disorders in term and premature neonates, anemic pregnant women, and fetuses in utero. The purposes of making these measurements are to; (1) identify patients who have hemolytic disorders, (2) characterize the severity of the hemolysis in each hemolytic patient, and (3) predict and prevent co-morbidities, thereby improving outcomes.

All neonates experience a downtrend in their hematocrit values immediately following the birth through normal falls in erythropoietin (Epo) production, transition to adult hemoglobin, and hemodilution with somatic growth. However, this drop is more pronounced in critically ill and preterm neonates and can lead to potentially pathologic anemia that impairs tissue oxygen delivery. In this review, we highlight the mechanisms underlying physiologic anemia and anemia of prematurity and briefly review the evidence for the treatment of anemia in the neonatal population, including the use of red blood cell transfusions, erythropoietic stimulating agents, and iron supplementation.

Mitochondria are highly-dynamic, membrane-bound organelles that generate most of the chemical energy needed to power the biochemical reactions in eukaryotic cells. These organelles also communicate with the nucleus and other cellular structures to help maintain somatic homeostasis, allow cellular adaptation to stress, and help maintain the developmental trajectory. Mitochondria also perform numerous other functions to support metabolic, energetic, and epigenetic regulation in our cells. There is increasing information on various disorders caused by defects in intrinsic mitochondrial or supporting nuclear genes, on different organ systems. In this review, we have summarized the ultrastructural morphology, structural components, our current understanding of the evolution, biogenesis, dynamics, function, clinical manifestations of mitochondrial dysfunction, and future possibilities. The implications of deficits in mitochondrial dynamics and signaling for embryo viability and offspring health are also explored. We present information from our own clinical and laboratory research in conjunction with information collected from an extensive search in the databases PubMed, EMBASE, and Scopus.

Objective: We previously reported improved neurodevelopment at 2 and 4 years among preterm infants treated with erythropoietin or darbepoetin, known as erythropoiesis-stimulating agents (ESAs). We now characterize longitudinal outcomes through 6 years. Methods: Children randomized to ESAs or placebo were evaluated at 6 years. Healthy-term children served as controls. Tests of cognition and executive function (EF) were performed. Results: Cognitive/EF scores remained similar between 4 and 6 years within each group (ESA: 43 children; placebo: 17 children; term: 21 children). ESA recipients scored higher than placebo on Full-Scale IQ (94.2 ± 18.6 vs. 81.6 ± 16.7, p = 0.022), and Performance IQ (97.3 ± 16.2 vs. 81.7 ± 15.2, = 0.005). Aggregate EF trended better for the ESA group. Term controls scored better than placebo on all measures. ESA and term controls scored similarly on cognitive and EF tests. Conclusion: ESA recipients had better outcomes than placebo recipients, and were similar to term children. ESAs may improve long-term cognition and executive function in preterm infants.

Background: Nucleated red blood cells (NRBC) are very uncommon in the blood of children and adults, but small numbers are not rare in neonates on the day of birth. Elevated NRBC counts in neonates can be seen following erythropoietin dosing. Limited studies in human neonates suggest the time-interval between erythropoietin dosing and the first appearance of NRBC in the blood (the “NRBC emergence-time”) is in excess of 24 hours. Methods: We made serial blood counts (Sysmex veterinary analyzer) on ten newborn lambs; five were dosed with darbepoetin (10 μg/kg), and five were dosed with a vehicle-control to assess the NRBC emergence time under relatively controlled laboratory conditions. Results: The first appearance of NRBC was at 24 h (2757 ± 3210 NRBC/μL vs. 0/μL in controls). Peak was 48-72 h (16,758 ± 8434/μL vs. 0/μL in controls), followed by fewer at 96 hours (7823 ± 7114/μL vs. 0/μL in controls). Similarly, reticulocytes peaked at 48-72 h (113,094 ± 3210/μL vs. 10,790 ± 5449/μL in controls), with no changes in platelets or leukocytes. Conclusion: The NRBC emergence time in newborn lambs is similar to reports from newborn humans. By extrapolation, if a neonate has a high NRBC at birth, the erythropoietic stimulus likely occurred within the interval 24 to perhaps 96+ hours prior to birth.