Upadhyay K, Talati A. Group B Streptococcal Infections in Neonates. Newborn 2022; 1 (1): 109-119. DOI: 10.5005/jp-journals-11002-0022.

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Abstract: Despite significant advances in preventive and therapeutic approaches, Group B streptococcus (GBS) still remains one of the most common causes of sepsis and meningitis in neonates. There is considerable variability in the immune responses that is related to microbial virulence, bacterial load, and immaturity of immune response system of the host. In this review, the mechanisms of GBS invasion and host–pathogen interactions are described. Understanding the host immune response to various bacterial components of GBS could help in refining our future strategies to mitigate the immune response and improve neonatal outcomes due to GBS sepsis.

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Key scientific associations: Antibiotics, bacterial components, group B streptococcus, group B streptococcus immune response, group B streptococcus vaccine, host–pathogen, inflammation, invasion, host-pathogen interactions, encapsulated Gram-positive, vaginal GBS colonization, premature rupture of membranes (PROM), gastrointestinal GBS colonization, and increased maternal age, adherence, proliferation, bacteremia, dissemination, systemic inflammatory response syndrome, serotypes, core genome, cross-linked peptidoglycans, surface proteins, polyanionic teichoic acid, lipoteichoic acid, histidine kinases, pore-forming toxins, alpha-like proteins, beta-proteins, serine-rich repeat proteins, leucine-rich repeat proteins, fibronectin-binding surface proteins, plasminogen-binding surface protein, adhesin, peptidase, capsular polysaccharides, capsular lipids, sialic acid O-acetylation, C-type lectin receptors, TLR2, TLR4, TRAF6, TLR8, early-onset disease, late-onset disease, intrapartum antibiotic prophylaxis.

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Donda K, Torres BA, Maheshwari A. Non-coding RNAs in Neonatal Necrotizing Enterocolitis. Newborn 2022; 1 (1): 120-130. DOI: 10.5005/jp-journals-11002-0012. Available in PubMed.

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Abstract: The incomplete understanding of the etiopathogenesis of necrotizing enterocolitis (NEC) contributes to the lack of timely diagnosis and limited therapeutic options. Non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression in various pathways that can modulate various physiological and pathological processes. Despite several studies revealing the role of ncRNAs in intestinal inflammatory diseases in adults, these remain largely unexplored in NEC. In this article, we review the information on ncRNAs that have been specifically identified in NEC or have been noted in other inflammatory bowel disorders that share some of the histopathological abnormalities seen frequently in NEC. We have assimilated the most current research findings on ncRNAs in intestinal diseases. This is an attempt to explore a novel field that has immense potential for future translational and clinical research in preventing, detecting, and treating NEC.

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Key scientific associations: Genetic predisposition, intestinal inflammation, necrotizing enterocolitis, neonates, non-coding RNA, spontaneous intestinal perforation, coding, non-coding RNAs, housekeeping ncRNAs, transfer RNAs, ribosomal RNAs, small nuclear RNAs, small nucleolar RNAs, regulatory ncRNAs, small ncRNAs, long ncRNAs, mid-size ncRNAs, promoter-associated small RNAs, transcription start site-associated RNAs, promoter upstream transcripts, circular RNAs, pyknons, microRNAs, piwi-interacting RNAs small interfering RNAs, lncRNAs, and circular RNAs, independent transcription units, primary RNAs, Drosha, exportin-5, RNA-induced silencing complex, Piwi interacting RNAs, piRNA induced silencing complex, transposon elements, small interfering RNAs, dicer, trans activating response RNA-binding protein, small nucleolar RNAs, exonic circRNAs, intronic circRNAs, exon-intronic circRNAs, intergenic circRNAs, and fusion circRNAs sense-lncRNAs, antisense-lncRNAs, or bidirectional lncRNAs, intronic-ncRNAs or long intervening/intergenic-ncRNAs, necroptosis, interferon-production regulator, miR-1246, miR-375, miR-124.

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Peng J, Ramatchandirin B, Pearah A, Maheshwari A, He L. Development and Functions of Mitochondria in Early Life. Newborn 2022; 1 (1): 131-141. DOI: 10.5005/jp-journals-11002-0013.

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Abstract: Mitochondria are highly dynamic organelles of bacterial origin in eukaryotic cells. These play a central role in metabolism and adenosine triphosphate (ATP) synthesis and in the production and regulation of reactive oxygen species (ROS). In addition to the generation of energy, mitochondria perform numerous other functions to support key developmental events such as fertilization during reproduction, oocyte maturation, and the development of the embryo. During embryonic and neonatal development, mitochondria may have important effects on metabolic, energetic, and epigenetic regulation, which may have significant short- and long-term effects on embryonic and offspring health. Hence, the environment, epigenome, and early-life regulation are all linked by mitochondrial integrity, communication, and metabolism.

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Key scientific associations: : early life, metabolism, mitochondria, mitochondrial dynamics, neonatal development, oocyte maturation, adenosine triphosphate, proton gradients, inner mitochondrial membrane, apoptosis, endosymbiotic alpha-proteobacterium, mitochondrial deoxyribonucleic acid, metabolic activity, stem cell differentiation, methionine metabolism, S-adenosylmethionine, methionine adenosyl transferases, Jarid2 deamylase, chromatin remodeling, histone acetyltransferases, sirtuin, mitochondrial inheritance, Leigh syndrome, neonatal cardiomyopathy, infantile leukodystrophy, lactic acidosis, horizontal transfer of mitochondria, necroptosis.

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Shakya P, Adhikari B, Nepal AS, Pandey P, Maheshwari A. Rotavirus Infection in Neonates and Young Infants. Newborn 2022; 1 (1): 142-150. DOI: 10.5005/jp-journals-11002-0014.

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Abstract: Rotavirus is the primary cause of acute, frequently severe gastroenteritis among growing premature neonates, young infants, and children under the age of five globally. It contains a double-stranded ribonucleic acid genome is a member of the Reoviridae family. In this review, we have discussed the structure and characteristics of the virus, the pathogenesis of rotaviral diarrhea, clinical features, methods of diagnosis, clinical management, and available vaccines. This article combines peer-reviewed evidence from our own clinical studies with results of an extensive literature search in the databases PubMed, EMBASE, and Scopus.

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Key scientific associations: : Diarrhea, double-stranded ribonucleic acid, gastroenteritis, nonenveloped virus, Reovirus, vaccine, World Health Organization, gastroenteritis, Reoviridae, viral proteins, nonstructural proteins, enterotoxin, viroplasm, capsid, spikes, glycoprotein, outer capsid shell, G serotypes, VP4 serotypes, P-subtyping, P-serotypes, enterocyte destruction, virus-encoded toxin, of enteric nervous stimulation, villus ischemia, capsid protein VP4, histo-blood group antigens, osmotically active infectious particles, villus blunting, crypt hyperplasia, vaccines, RotaShield, Rotateq, Rotarix.

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Rao RB. Neonatal Hypoglycemia. Newborn 2022; 1 (1): 151-157. DOI: 10.5005/jp-journals-11002-0011.

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Abstract: Hypoglycemia is the most common metabolic problem in the neonatal period with a potential to cause brain injury. However, there are controversies in diagnosis, significance, and treatment of neonatal hypoglycemia. Several large-scale prospective and retrospective studies have reported the impact of neonatal hypoglycemia on neurodevelopment in high-risk infants. Significance of short-term hypoglycemia on neurodevelopment in healthy infants remains unresolved. There are also concerns that rapid correction of hypoglycemia may worsen brain injury. Conflicting recommendations from professional societies have further muddied the field. This review examines the current knowledge on the epidemiology of neonatal hypoglycemia, its impact on neurodevelopment, current screening and treatment recommendations, and the emerging role of dextrose gel for management of neonatal hypoglycemia. 

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Key scientific associations: Hypoglycemia, neonatology, neurodevelopment, newborn, newborn infant, preterm infants, neurodevelopment, dextrose, glycogenolysis, gluconeogenesis, hyperinsulinism, neuronal injury, anterior cingulate, orbital cortex, neurosensory impairment, processing difficulty, Bayley Scales of Infant Development III (BSID-III), vision screening, global motion perception, executive function, cognitive, executive, visual, motor function, HypoEXIT trial.

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Dillard JA, Murray C, Mathur AA. New Therapeutic Targets in Neonatal Pulmonary Hypertension. Newborn 2022; 1 (1): 158-169. DOI: 10.5005/jp-journals-11002-0015.

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Abstract: Hypoglycemia is the most common metabolic problem in the neonatal period with a potential to cause brain injury. However, there are controversies in diagnosis, significance, and treatment of neonatal hypoglycemia. Several large-scale prospective and retrospective studies have reported the impact of neonatal hypoglycemia on neurodevelopment in high-risk infants. Significance of short-term hypoglycemia on neurodevelopment in healthy infants remains unresolved. There are also concerns that rapid correction of hypoglycemia may worsen brain injury. Conflicting recommendations from professional societies have further muddied the field. This review examines the current knowledge on the epidemiology of neonatal hypoglycemia, its impact on neurodevelopment, current screening and treatment recommendations, and the emerging role of dextrose gel for management of neonatal hypoglycemia. 

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Key scientific associations: Extracorporeal membrane oxygenation, Neonate, Persistent pulmonary hypertension of the newborn, Pulmonary hypertension, Newborn, neonate, inhaled nitric oxide, extracorporeal membrane oxygenation, soluble guanylate cyclase stimulators, prostacyclin, phosphodiesterase 3, 4, and 5 inhibitors, rho-kinase inhibitors, endothelin receptor blockers, PPARγ agonists, antioxidants, pulmonary vascular resistance, pulmonary blood flow, right-to-left shunting, foramen ovale, ductus arteriosus, soluble guanylate cyclase, cyclic guanosine monophosphate, BAY 41-2272, BAY 41-8543, sildenafil, BAY 63-2561, riociguat, PATENT–CHILD study, PVR/systemic vascular resistance ratio, right ventricular hypertrophy, BAY 58-2667, cinaciguat, COMPOSE studies, prostacyclin, adenylate cyclase, prostacyclin, iloprost, oxygenation index, treprostinil, cyclic nucleotide phosphodiesterase, PDE3, PDE4, PDE5, inotropic, lusitropic, vasodilatory, piclamilast, roflumilast, tadalafil, rho-kinase, Y-27632, HA-1077, ROCK inhibitor, fasudil, endothelin, bosentan, FUTURE-4 trial, peroxisome proliferator-activated receptors, rosiglitazone, peroxynitrite, N-acetylcysteine, superoxide dismutase.

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Roychaudhuri S, Grewal G, Vijayashankar SS, Lavoie P, Maheshwari A. Necrotizing Enterocolitis Associated with Congenital Heart Disease - A Review Article. Newborn 2022; 1 (1): 170-176. DOI: 10.5005/jp-journals-11002-0016.

 

Abstract: Necrotizing enterocolitis (NEC) is a relatively rare but devastating entity associated classically with the preterm cohort in the neonatal intensive care unit. Preterm and term babies with congenital heart disease are at risk of a number of comorbidities because of the hemodynamic derangements due to a structurally abnormal heart and the corrective procedures adopted. Necrotizing enterocolitis is one of the dreaded complications associated with this cohort and impacts the course of these babies in the hospital in a major way. A large majority of term babies with NEC are in the backdrop of a significant congenital cardiac lesion. This review article summarizes the literature and elaborates this entity including its specific features, risk factors associated with its causality, histopathology and related aspects of hemodynamics, and feeding in this vulnerable population. It also provides insight into modifiable risk factors and early markers of detection of gut necrosis to facilitate prevention and early detection. It highlights the subtle but definite difference in outcome variables to help physicians enable the parents of babies with heart disease to develop a better understanding of the entity and its expected course while counseling. 

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Key scientific associations: Congenital heart disease, Necrotizing enterocolitis, Neonatal mortality, Preterm newborns, ischemia, cardiogenic NEC, post-operative period, necrosis, bacterial load, hypoperfusion, hypoplastic right ventricle syndrome, Risk Adjustment for Congenital Heart Surgery (RACHS-1) criteria, ischemic-reperfusion injury, mesenteric blood flow velocity, vascular resistance, standardized feeding protocols, bowel ultrasonography, splanchnic NIRS, fecal calprotectin.

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Mishra V, Mathur AA, Mohamed S, Maheshwari A. Role of Near-infrared Spectroscopy in the Diagnosis and Assessment of Necrotizing Enterocolitis. Newborn 2022; 1 (1): 177-181. DOI: 10.5005/jp-journals-11002-0001.

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Abstract: Near-infrared spectroscopy (NIRS) is a noninvasive, bedside diagnostic tool that could assist in the early diagnosis of necrotizing enterocolitis (NEC) in preterm neonates. NIRS is a safe and effective clinical tool in the neonatal intensive care unit to detect abnormal alterations in tissue perfusion and oxygenation. In addition, NIRS could also detect the complications of NEC, such as bowel necrosis and perforation. NEC is the most common gastrointestinal complication associated with preterm birth and critically ill infants. It is observed in 6–10% of preterm neonates, weighing below 1500 g, leading to considerable morbidity, mortality, and healthcare cost burden. The mortality rate ranges from 20 to 30%, highest in NEC infants undergoing surgery. NIRS is a promising diagnostic modality that could facilitate the early diagnosis of NEC and early detection of complications alone or with the imaging modalities.

 

Key scientific associations: Near-infrared spectroscopy, necrotizing enterocolitis, neonatology, newborn, preterm infant, 

near-infrared radiation, hemoglobin oxygenation, tissue oxygenation, light-emitting diode, photons, oxygenated hemoglobin, deoxygenated hemoglobin, fractional tissue oxygen extraction, splanchnic oxygenation, cerebral autoregulation, supra-umbilical oxygen saturation, infra-umbilical oxygen saturation, hypoxic-ischemic encephalopathy, Mepitel barrier, supraumbilical probe.

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Mishra V, Cuna A, Singh R, Schwartz DM, Chan S, Maheshwari A. Imaging for Diagnosis and Assessment of Necrotizing Enterocolitis. Newborn 2022; 1 (1): 182-189. DOI: 10.5005/jp-journals-11002-0002.

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Abstract: Necrotizing enterocolitis (NEC) is inflammatory bowel necrosis of preterm and critically ill infants. The disease is seen in 6-10% of preterm infants who weigh less than 1500 g at birth and carries considerable morbidity, mortality, and healthcare cost burden. Efforts focused on timely mitigation remain restricted due to challenges in early diagnosis as clinical features, and available laboratory tests remain nonspecific until late in the disease. There is renewed interest in the radiological and sonographic assessment of intestinal diseases due to technological advances making them safe, cost-efficient, and supporting Web-based transmission of images, thereby reducing time to diagnosis by disease experts. Most of our experience has been with plain abdominal radiography, which shows characteristic features such as pneumatosis intestinalis in up to 50–60% of patients. Many patients with advanced disease may also show features such as portal venous gas and pneumoperitoneum. Unfortunately, these features are not seen consistently in patients with early, treatable conditions, and hence, there has been an unfulfilled need for additional imaging modalities. In recent years, abdominal ultrasound (AUS) has emerged as a readily available, noninvasive imaging tool that may be a valuable adjunct to plain radiographs for evaluating NEC. AUS can allow real-time assessment of vascular perfusion, bowel wall thickness, with higher sensitivity in detecting pneumatosis, altered peristalsis, and characteristics of the peritoneal fluid. Several other modalities, such as contrast-enhanced ultrasound (CEUS), magnetic resonance imaging (MRI), and near-infrared spectroscopy (NIRS), are also emerging. In this article, we have reviewed the available imaging options for NEC evaluation.

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Key scientific associations: Diagnostic imaging, neonatology, prematurity, preterm neonate, ultrasonography, pneumatosis intestinalis, intraluminal air, pneumoperitoneum, football sign, falciform ligament sign, hypoechoic rim, central echogenic focus, bowel wall thickness, circle sign, reverberation artifacts, portal venous pneumatosis, dendriform granular pattern, valvulae conniventes, greyscale zebra pattern, herringbone pattern, ring-shaped signals, echogenic ascites, International Neonatal Consortium, flash artifacts, contrast-enhanced ultrasound, magnetic resonance colonography, dynamic contrast-enhanced MRI, near-infrared spectroscopy, splanchnic ischemia, regional splanchnic oxygen saturation, fractional tissue oxygen extraction, Broad optical spectroscopy

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Pillai SS, Foster CA, Ashraf AP. Approach to Neonatal Hypocalcemia. Newborn 2022; 1 (1): 190-196. DOI: 10.5005/jp-journals-11002-0017.

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Abstract: Hypocalcemia in neonates is defined as total serum calcium concentration less than 7.5–8 mg/dL and/or ionized calcium less than 4.4 mg/dL in neonates (>1500 g) and total serum calcium concentration less than 7 mg/dL or ionized calcium less than 3.6 mg/dL in low-birth-weight neonates (<1500 g). About 80% of the calcium transfer across the placenta occurs in the last trimester. Parathyroid hormone-related peptide (PTHrP) regulates the positive calcium balance in the placenta. Postpartum serum calcium level in neonates depends on an intricate relationship between PTH and renal and skeletal factors. Based on the timing of the presentation, hypocalcemia can be early onset (develops in the first 72 hours of life) and late onset (occurs after 72 hours of life). Causes of early-onset hypocalcemia include prematurity, SGA, IUGR, birth asphyxia, diabetes mellitus, or toxemia in the mother. Late-onset neonatal hypocalcemia may be caused by increased dietary phosphate content, neonatal vitamin D deficiency, hypomagnesemia, hypoparathyroidism, or parathyroid hormone resistance. We present a neonate with hypocalcemia due to transient hypoparathyroidism secondary to maternal adenoma. A thorough history and physical examination are essential to identify at-risk asymptomatic infants who need screening for hypocalcemia. Neonatal hypocalcemia can be a serious event and can cause serious morbidity and mortality. Majority of the early as well as transient late neonatal hypocalcemia resolves completely, while lifelong treatment may be required in some cases depending on the etiology.

 

Key scientific associations: Calcium, hypocalcemia, neonate, newborn, parathyroid hormone-related peptide, early onset hypocalmemia, late onset hypocalcemia, increased dietary phosphate content, neonatal vitamin D deficiency, hypomagnesemia, hypoparathyroidism, parathyroid hormone resistance, serum 25 hydroxy vitamin D, parathyroid hormone, calcitonin, calcium sensing receptors, calcitriol, renal proximal tubule, calcitonin, parafollicular cells of thyroid gland, bone resorption, transmembrane calcium selective channel TRPV6, calbindin D9k, plasma membrane calcium-ATPase, calcidiol, melastatin 6 (TRPM6), CLDN16, DiGeorge syndrome, maternal hyperparathyroidism, GMC2, CaSR, GNA11 mutations, X-linked SOX3 mutations, 22q deletion Syndrome, CHARGE association (CHD7), autoimmune polyglandular syndrome type 1, sensorineural deafness, renal dysplasia (HDR) syndrome, mitochondrial cytopathies, Sanjad-Sakati, Kenney-Caffey syndromes, pseudohypoparathyroidism with end-organ PTH resistance, renal dysplasia,  obstructive uropathy, permanent pseudohypoparathyroidism, Albright’s hereditary osteodystrophy, pyloric spasm.

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Spence KL, Salter EK. Rethinking the Paradigm: The Evolving Care of Children with Trisomy 13 and 18. Newborn 2022; 1 (1): 197-200. DOI: 10.5005/jp-journals-11002-0007.

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Abstract: A chromosomal evaluation should be used to provide better care for a child and their family, not limit it. However, in many pediatric institutions, the diagnosis of a chromosomal abnormality automatically circumscribes the medical and surgical options made available to the family. For example, alongside many other comorbidities (including severe cognitive impairment), infants diagnosed with trisomy 13 or 18 (T13/18) often have cognitive heart defects (e.g., atrial or ventricular septal defects, patent ductus arteriosus, atrioventricular septal defects) that can be successfully repaired or palliated in the general population. However, because T13/18 have historically been considered “lethal” diagnoses or “incompatible with life”, surgical correction of these defects is not frequently offered, and instead infants with these diagnoses are managed with a noninterventionist, “comfort care” approach in which the infant is simply allowed to expire after birth. In recent years, however, more data have emerged from centers that regularly pursue medical and surgical interventions in this population, demonstrating improved outcomes in both quality and quantity of life. Simultaneously, the pediatric ethics literature has argued that treatment decisions for infants with T13/18 are frequently informed by unfounded biases concerning disability and quality of life. Now that neonatology is equipped with improved medical and ethical evidence, the practice of categorically excluding infants with a T13/18 diagnosis from life-saving interventions should be challenged, and instead, parents of these infants should be offered targeted interventions, including corrective and palliative procedures, and included in the process of shared decision-making about which interventions best meet the family’s goals of care.

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Key scientific associations: Ethics, trisomy 13, trisomy 18, trisomy 21, newborn, neonate, chromosomal abnormality, comfort care, limb malformations, growth restriction, rocker bottom feet, myelomeningocele, developmental disability, hearing deficiencies, vision deficiencies, communication difficulties, disability paradox, expectant management of cardiac interventions, Baby Doe Regulations of 1984, pulmonary hypertension, repair of cardiac defects.

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Khashu M, Dame C, Lavoie PM, De Plaen IG, Garg PM, Sampath V, Malhotra A, Caplan MD, Kumar P, Agrawal PB, Buonocore G, Christensen RD, Maheshwari A. Current Understanding of Transfusion-associated Necrotizing Enterocolitis: Review of Clinical and Experimental Studies and a Call for More Definitive Evidence. Newborn 2022; 1 (1): 201-208. DOI: 10.5005/jp-journals-11002-0005. Available in PubMed. 

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Abstract: Introduction: The association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC), so-called transfusion-associated NEC (ta-NEC), was first described in 1987. However, further work is needed to confirm a causal relationship, elucidate underlying mechanisms, and develop possible strategies for prevention. We performed an extensive literature search in the databases PubMed, EMBASE, and Scopus. Areas covered: Although multiple retrospective human studies have strongly suggested an association between blood transfusions and subsequent occurrence of NEC, meta-analyses of randomized controlled trials (RCTs) testing RBC transfusion thresholds or the use of recombinant erythropoiesis-stimulating growth factors did not confirm an association of anemia with ta-NEC. These conflicting data necessitated the development of an animal model to elucidate mechanisms and causal factors. Data from this recent mouse model of ta-NEC highlighted the importance of sequential exposure to severe anemia followed by transfusion for development of ta-NEC. Expert opinion: This review summarizes current human and experimental data, highlights open questions, and suggests avenues for further research aimed at preventing ta-NEC in preterm infants. Further studies are required to delineate whether there is a tipping point, in terms of the level and duration of anemia, and to develop an effective strategy for blood management and the quality of RBC transfusions.

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Key scientific associations: Anemia, necrotizing enterocolitis, preterm infants, ta-NEC, TANEC, TRAGI, transfusion, newborn, neonate, premature, severe anemia, transfused, transfusion-associated NEC, recombinant erythropoiesis-stimulating factors, systematically review, meta-analysis, ETTNO trial, TOP trial, recombinant human erythropoietin, darbepoietin, splanchnic fractional tissue oxygen extraction, fatty acid-binding protein 2, monocyte/macrophage infiltration, Toll-like receptor 4-mediated signaling, redox cycling, NF-κB pathway, splanchnic autoregulation, transient intestinal ischemia, preterm erythropoietin neuroprotection trial (PENUT), WHEAT (withholding enteral feeds around packed red cell transfusion) study, feeding during red cell transfusion (FEEDUR) trial, lactoferrin, L-arginine.

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