Maheshwari A, Singh R, Christensen RD. Care of the Newly Born Needs to Begin Prior to Birth and to Continue then After. Newborn 2022; 1 (2):iv-v. DOI: 10.5005/newborn-1-2-iv.

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Morotti F, Candela GF, Martellosio G, Serana F, Micheletti M, Brugnoni D, Risso FM, Motta M. Automated Cell Counter-derived Neutrophil Cell Population Data by VCS Technology as a Marker of Early-onset Neonatal Sepsis. Newborn 2022; 1 (2):209-214. DOI: 10.5005/jp-journals-11002-0030.

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Abstract: Aim: Early-onset neonatal sepsis (EONS) occurring within the first 72 hours after birth is a common, life-threatening disease in neonatal intensive care units (NICUs). The limited accuracy of diagnostic tools makes the diagnosis of EONS difficult, and the quest for new markers remains open. Automated hematology analyzer-derived neutrophil cell population data (N-CPD) have been identified as a potential marker of neonatal sepsis, but their role for EONS has not been elucidated yet. Our aim is to explore the role of automated hematology analyzer-derived N-CPD as a marker of EONS. Methods: We prospectively evaluated a cohort of 289 neonates admitted to the NICU with clinical signs of sepsis, and checked if N-CPD from the Beckman Coulter UniCel DxH 800 device could help identify those who would develop culture-proven EONS. Clinical characteristics, sepsis markers, blood culture results, and N-CPD were recorded. The diagnostic accuracy of N-CPD was tested using receiver-operator curves (ROCs). Results: Receiver-operator curves of the standard deviation of neutrophil volume (SD-V) showed moderate accuracy in identifying EONS (AUC 0.74), with a high negative predictive value (NPV 98.6%) for cut-off values >21.76 arbitrary units. Accuracy was higher with VCS at 12–48 hours of life (AUC 0.8). Standard deviation of neutrophil volume accuracy was independent from gestational age (GA), birth weight, and timing of test execution (OR 1.14, p = 0.002; AUC 0.71). Conclusion and significance: Our study confirms the role of N-VCS in the diagnostic workup for EONS. High NPV values may be useful as they suggest a role as an adjunctive marker useful for ruling-out EONS and support early empirical antibiotic withdrawal.

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Key scientific associations: Newborn, neonate, diagnostic tools, markers, automated hematology analyzer-derived neutrophil cell population data, receiver-operator curves, diagnostic accuracy, neutrophil volume accuracy, cerebrospinal fluid bacterial culture, late-onset neonatal sepsis, immature-to-total ratio, C-reactive protein, absolute neutrophil count, biophysical properties of leukocytes, direct current impedance, radio frequency opacity, conductivity, cytoplasmic granularity, median angle light scatter, group B Streptococci, coagulase-negative Streptococcus, Enterococcus faecalis, Gram-negative bacteria, Swets classification.

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Shukla VV, Carlo WA. Risk Prediction for Stillbirth and Neonatal Mortality in Low-resource Settings. Newborn 2022; 1 (2):215-218. DOI: 10.5005/jp-journals-11002-0034. Available in PubMed.

Abstract: High stillbirth and neonatal mortality are major public health problems, particularly in low-resource settings in low- and middle-income countries (LMIC). Despite sustained efforts by national and international organizations over the last several decades, quality intrapartum and neonatal care is not universally available, especially in these low-resource settings. A few studies identify risk factors for adverse perinatal outcomes in low-resource settings in LMICs. This review highlights the evidence of risk prediction for stillbirth and neonatal death. Evidence using advanced machine-learning statistical models built on data from low-resource settings in LMICs suggests that the predictive accuracy for intrapartum stillbirth and neonatal mortality using prenatal and pre-delivery data is low. Models with delivery and post-delivery data have good predictive accuracy of the risk for neonatal mortality. Birth weight is the most important predictor of neonatal mortality. Further validation and testing of the models in other low-resource settings and subsequent development and testing of possible interventions could advance the field.

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Key scientific associations: Newborn, neonate, perinatal, stillbirth, neonatal mortality, low- and middle-income countries, LMIC, risk stratification, risk prediction, outcome prediction models, machine-learning models, predictive accuracies, validation data.

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Romano-Keeler J, Sun J. The First 1000 Days: Assembly of the Neonatal Microbiome and Its Impact on Health Outcomes. Newborn 2022; 1 (2):219-226. DOI: 10.5005/jp-journals-11002-0028. Available in PubMed.

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Abstract: Early life microbial colonization is critical for the development of the immune system, postnatal growth, and long-term health and disease. The dynamic and nascent microbiomes of children are highly individualized and are characterized by low bacterial diversity. Any disruptions in microbial colonization can contribute to shifts in normal microbial colonization that persist past the first 1,000 days of life and result in an intestinal dysbiosis. Here, we focus on microbiome-host interactions during fetal, newborn, and infant microbiome development. We summarize the roles of bacterial communities in fetal development and adverse health outcomes due to dysbiosis. We also discuss how internal and external factors program the microbiome’s metabolic machinery as it evolves into an adult-like microbiome. Finally, we discuss the limits of current studies and future directions. Studies on early-life microbiome will be critical for a better understanding of childhood health and diseases, as well as restorative methods in prevention and treatment of diseases in adulthood.

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Key scientific associations: Newborn, neonate, microbial colonization, immune system, postnatal growth, microbiome-host interactions, bacterial communities, dysbiosis, bacteria, fungi, immunity, microbiome, necrotizing enterocolitis, probiotics, viromes, Developmental Origins of Health and Disease, DOHad, Barker hypothesis, bacterial diversity, mycobiome, archaea, archaeome, bacteriophage, insulin resistance, dyslipidemia, hypertension, Bacteroides longum subspecies infantis, Lactobacillus, gestational diabetes mellitus, fetal microbiome, Gram-negative intracellular organisms, chorioamnionitis, Bray Curtis similarity indices, atopy, Enterobacter, Enterococcus, Staphylococcus, prebiotic, toll-like receptors, The Environmental Determinants of Diabetes in the Young study (TEDDY), bacterial diversity, bacterial richness, firmicutes, KOALA Birth Cohort, hygiene hypothesis, epigenetic, posttranscriptional histone alterations, chromatin restructuring, non-coding RNA.

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Grauerholz KR. Tasked for Compassion: Initiating Reproductive Grief Care in the Neonatal Intensive Care Unit. Newborn 2022; 1 (2):227-232. DOI: 10.5005/jp-journals-11002-0026.

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Abstract: The experience of parenting a premature or ill infant in the neonatal intensive care unit (NICU) can be overwhelming and traumatic. Parents who have previously endured a reproductive loss may find that an accumulation of escalating distress related to nurturing a neonate while receiving care in intensive care compounded with lingering grief from a prior perinatal loss can overwhelm their capability to cope. The ambiguous nature of perinatal loss and societal disenfranchisement of the grief often results in a prolonged or complicated bereavement trajectory which can inhibit bonding, mental health, and physical wellness. The frequent contact and perinatal conversations between parents and clinicians provide opportunities for essential discussions about emotional vigor, grief, and bereavement. A review of the literature and current research found that initiating conversations and care modalities that facilitate Worden’s “tasks of grieving” can foster a necessary healing pattern for bereaved parents. These efforts will theoretically nurture parent–child bonding and promote desirable neonatal outcomes.

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Key scientific associations: Neonate, newborn, reproductive loss, perinatal loss, societal disenfranchisement, tasks of grieving, pregnancy loss, infertility, perinatal palliative care, perinatal bereavement, reproductive morbidity, grieving trajectory, disenfranchisement, reproductive bereavement care, family enfranchisement of, grief, early pregnancy loss, ontological death, sonography photographs, bereavement education, relational efficacy, occupational satisfaction, parent provider alliances, neonatal bonding experiences.

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Maheshwari A. Jilling T. Major Chromosomal Abnormalities and Necrotizing Enterocolitis: Is there a Link? Newborn 2022; 1 (2):233-237. DOI: 10.5005/jp-journals-11002-0032.

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Abstract: Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis seen in premature infants. The etiopathogenesis of NEC is unclear, but increasing information suggests that genetic factors may alter the susceptibility to NEC and/or its severity, its clinical and histopathological manifestations, and if surgery is needed, of an adverse postoperative course and outcome. This review draws from existing studies focused on individual genes and others based on microarray-based high-throughput discovery techniques. We have included evidence from our own studies and from an extensive literature search in the databases PubMed, EMBASE, and Scopus. To avoid bias in the identification of studies, keywords were short-listed a priori from anecdotal experience and PubMed’s Medical Subject Heading (MeSH) thesaurus.

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Key scientific associations: Premature, preterm, gestation, numerical chromosomal disorders, trisomy, monosomy, triploidy, Klinefelter syndrome, Turner syndrome, trisomy 13, trisomy 18, trisomy 21, deletions, duplication, translocation, balanced translocation, unbalanced translocation, Robertsonian, centromeres, inversions, paracentric, pericentric, isochromosome, dicentric chromosome, ring chromosome, extra-numerary Y-chromosome, Klinefelter syndrome, partial trisomies, partial monosomies, Germ line chromosomal abnormality, somatic chromosomal abnormality, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Turner syndrome, chromosome 1, ATG4C, FOXD3, ITGB3BP, chromosome 6, ezrin, superoxide dismutase 2, SOD2, NADPH oxidase 3, NOX3, Mitogen-Activated Protein Kinase Kinase Kinase 4, MAP3K4, 22q11 deletion, DiGeorge syndrome

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Mishra V, Panigrahi N, Rao A, Maheshwari A, Huisman TAGM. Neurological Abnormalities in Infants of Mothers with Diabetes Mellitus. Newborn 2022; 1 (2):238-244. DOI: 10.5005/jp-journals-11002-0033.

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Abstract: Fetal anomalies, neurocognitive disorders, and perinatal mortality rates are higher in infants of diabetic mothers (IDMs) than in infants of mothers without diabetes. The pathology of these defects is significantly influenced by maternal glucose control and the onset of diabetes during pregnancy. Maternal hyperglycemia, abnormal inflammatory response, and fetal oxidative stress contribute to the pathogenesis of neurological deficits in IDMs. Pregestational diabetes mellitus (PGDM) have a higher incidence of congenital neurologic structural anomalies than gestational diabetes mellitus (GDM). The assessment of neurodevelopmental impairment in IDMs is confounded by perinatal factors, including birth asphyxia, acute and chronic metabolic insults, and iron deficiency. The incidence of these defects tends to reduce with appropriate antenatal care and maternal glycemic control. We discuss the structural neurologic malformations, cognitive disorders, motor deficits, and psychosocial disorders in the offspring of diabetic mothers.

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Key scientific associations: Neonate, newborn, World Health Organization, diabetes mellitus, pregestational diabetes mellitus, gestational diabetes, fetal anomalies, neurobehavioral abnormalities, infants of diabetic mothers, maternal glycemic control, cognitive impairment, motor disorders, psychosocial disorders, motor function, attention span, T-cells, cytokines, reactive oxygen species, free radicals, mitochondrial dysfunction, neurotrophin, nerve growth factor, brain-derived neurotrophin, neurotrophin-3, neurotrophin-4/5, angiogenesis, antioxidant, brain-derived neurotrophic factor, cerebral cortex, hippocampus, neuroplasticity, microcephaly, cysts, hydrocephalus, neural tube defects, caudal regression syndrome, advanced glycosylation end-products, diabetic embryopathy, glycosylated hemoglobin levels, oxidative stress, nitrosative stress, placentation, apoptosis, teratogenic, FT0, TCF7L2, LEP, anencephaly, encephalocele, meningomyelocele, holoprosencephaly, caudal regression syndrome, EUROCAT registries, spinal-pelvic instability, hip dislocation, popliteal webbing, extrahepatic biliary atresia, VACTERL, communication, learning, motor coordination, problem-solving, basal ganglia, amygdala, hippocampus, synaptic plasticity, insulin, insulin-like growth factors, cerebellar size, Purkinje cells, granular cells, autism spectrum disorder, schizophrenia, cerebellum.

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Sharma G, Sharma RR, Maheshwari A. Approach to Neonatal Alloimmune Thrombocytopenia: The Perspective from a Transfusion Medicine Service. Newborn 2022; 1 (2):245-253. DOI: 10.5005/jp-journals-11002-0031.

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Abstract: Neonatal Alloimmune Thrombocytopenia (NAIT) is an important hematological disorder in neonates. The pregnant mother’s immune system gets sensitized to antigens expressed on fetal platelets that have been inherited from the father, and begins producing specific alloantibodies against these antigens. Some of these antibodies get transported across the placenta into the baby and can damage/destroy platelets to cause fetal/neonatal thrombocytopenia. Many of these fetuses/infants develop major clinical complications such as intracranial hemorrhages.In this article, we describe normal platelet counts in neonates, the pathogenesis and epidemiology of NAIT, specific platelet antigens that have been identified as targets in NAIT, and the approach for laboratory diagnosis of NAIT. From the perspective of a transfusion medicine service, there are two targets:(a) to identify differences in the antigenic profiles of the platelets of the mother and her fetus/infant; and (b) to detect alloantibodies in the maternal serum that may be specifically reactive to these platelet antigens. Early identification of NAIT can help timely institution of appropriate treatment. In this project, we reviewed the laboratory profiles of infants who were diagnosed to have NAIT at our own institution and also mined the literature in the databases EMBASE, PubMed, and Scopus.

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Key scientific associations: Newborn, platelets, antibody, gestation, intrauterine infections, Apgar scores, hemorrhages, bleeding, alloantigens, human leukocyte antigen, glycoproteins, syncytiotrophoblast microparticles, syncytiotrophoblasts-derived microparticles, glycoproteins, single nucleotide polymorphisms, alloantibodies, platelet-specific antigens, plextin semaphorins, glycosylphosphatidylinositol, Nak, Platelet suspension immunofluorescence test, ABO antigens, Glycoprotein IV, human leukocyte antigens, Platelet suspension immunofluorescence test, Antigen capture assays, Antigen Capture Elisa, Modified Antigen Capture Elisa, Monoclonal Antibody-specific Immobilization of Platelet Antigen, Radioimmunoprecipitation, Beads-based technologies, Immune-complex capture fluorescence analysis, Fluorescent bead-based platelet antibody detection method, platelet genotyping, variable number tandem repeat analysis, Sequence Specific Primer-Polymerase Chain reaction, Restriction fragment Length Polymorphism-Polymerase Chain reaction, TaqMan Real Time-Polymerase Chain reaction

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Grewal GK, Osiovich H, Schreiber R. Neonatal Acute Liver Failure. Newborn 2022; 1 (2):254-262. DOI: 10.5005/jp-journals-11002-0029.

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Abstract: Acute liver failure is a rare event in the newborn period yet early recognition in the neonatal intensive care setting is essential for best outcome. Neonatal acute liver failure (NALF) is distinct from acute liver failure in older children and adults having different etiologies, presentation, and unique treatment interventions. There is a paucity of literature regarding NALF and several newly identified conditions merit discussion. Herein we report three cases of liver failure who were admitted to our neonatal intensive care unit and review the diagnostic approach and management of liver failure in this age group.

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Key scientific associations: Newborn, neonate, diagnosis, enterovirus, gestational alloimmune liver disease, hemophagocytic lymphohistocytosis, neonatal acute liver failure, neonatal disease, KRT8, keratin 8, parechovirus, mitochondrial gene sequencing, reversed myeloid: erythroid ratio, erythroid hyperplasia, ferritin, soluble IL, CD136, galactosemia, tyrosinemia, mitochondrial depletion syndromes, DGUOK, neonatal hemochromatosis, siderosis, secondary hemochromatosis, fetal-onset liver failure, acyclovir, neonatal enterovirus sepsis, pancreatitis, adrenal hemorrhage, neonatal cirrhotic liver disease, pleconaril, allogeneic hematopoietic cell transplantation.

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