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JNB Jan-Mar 2023 V2 N1 Cover.tiff

A composite PDF file containing all the articles in volume 2, issue 1; January-March 2023 is provided here. 

The references (with links) to all the individual articles are listed below:

Maheshwari A, Lui K, Motta M. Neonates are not adults; there are unusual pathogens, limitations in immunity, need for new ways to treat, and to monitor for adverse effects. Newborn 2023;2(1):iv-vii. DOI: 10.5005/newborn-2-1-iv.


Motta M, Aversa S, Morotti F, et al. Extrauterine Growth Restriction in Preterm Very Low Birth Weight Infants: The Use of a Web-based System designed for Computerized prescribing of Parenteral Nutrition in Neonatal Intensive Care. Newborn 2023; 2 (1):1-10. DOI: 10.5005/jp-journals-11002-0052.


Abstract: Aim: Extrauterine growth restriction (EUGR) is a multi-factorial condition that may lead to long-term consequences for preterm infants. Providing adequate nutrition is one of the keys to ameliorating growth. Technology can help clinicians with powerful tools. We evaluate the impact of a web-based software specifically designed for neonatal parenteral nutrition (PN) prescription on EUGR in a cohort of very low birth weight (VLBW) infants; Materials and methods: We retrospectively analyzed anthropometric measurements (AMs) and comorbidities in a cohort of 119 VLBW infants treated with PN for at least 5 consecutive days. INTERGROWTH-21st standards were used to identify small for gestational age (SGA, birth weight < 10th centile) infants and to define EUGR. EUGR was defined as “cross-sectional” (AMs < 10th percentile at discharge) and “longitudinal” (loss in AMs Z-score from birth to discharge > 1 standard deviation [SD]); Results: Nutritional intakes were consistent with current available nutritional guidelines. There were significant differences in the measured incidence of EUGR depending on the adopted definition. The longitudinal definition appeared to be the most appropriate than the cross-sectional one for identifying postnatal growth failure in preterm infants. Lower lipid intake and longer durations of PN were risk factors for poor growth in weight and head circumference (HC). Metabolic disorders, such as cholestasis, hyperglycemia, and hypertriglyceridemia, had stronger links with lower AMs and longer PN needs than just the nutritional intakes. No relationships were observed between the most of comorbidities associated with prematurity and EUGR; Conclusions: A web-based system for the prescription of neonatal PN seems to be useful for ensuring adequate intakes in preterm infants. Further studies with larger sample sizes could be designed for evaluating the application of this software within a neonatal network and its effect on postnatal growth; Clinical significance: The use of an electronic prescribing system designed for neonatal care can help neonatologists in giving VLBW infants the correct intake of nutrients.

Key scientific associations: Neonate, newborn, infant, small-for-gestation, extra-uterine growth restriction, preterm, premature, web-based software, anthropometric measurements, INTERGROWTH-21st standards, cross-sectional, z-score, cholestasis, hyperglycemia, hypertriglyceridemia, electronic prescribing system, computerized prescribing, population-based study, cholestasis, hypertriglyceridemia, hyperglycemia, hypophosphatemia, neonatal sepsis, necrotizing enterocolitis, Vermont-Oxford network, bronchopulmonary dysplasia, retinopathy of prematurity, intra-ventricular hemorrhage, patent ductus arteriosus, hypertriglyceridemia, logistic regression.


Tyagi M, Guaragni B, Dendi A, et al. Use of Cryoprecipitate in Newborn Infants. Newborn 2023; 2(1): 11–18. DOI: 10.5005/jp-journals-11002-0045.

Abstract: Cryoprecipitate is a transfusion blood product derived from fresh–frozen plasma, comprised mainly of the insoluble precipitate that gravitates to the bottom of the container when plasma is thawed and refrozen. It is highly enriched in coagulation factors I (fibrinogen), VIII, and XIII; von Willebrand factor (vWF); and fibronectin. In this article, we have reviewed currently available information on the preparation, properties, and clinical importance of cryoprecipitate in treating critically ill neonates. We have searched extensively in the databases PubMed, Embase, and Scopus after short-listing keywords to describe the current relevance of cryoprecipitate.

Key scientific associationsNewborn, neonate, infant, Cryo, cryoprecipitated antihemophilic factor, transfusion product, plasma, factor I fibrinogen, factor VIII, factor XIII, von Willebrand factor, fibronectin, hemophilia A, precipitate, fresh frozen plasma, platelet-depleted plasma, American Association of Blood Banks, citrate-phosphate-dextrose-adenine, FP24, platelet membrane microparticles, glycoproteins, alloimmunoreactivity, amotosalen, ultraviolet light, hypofibrogenemia, dysfibrogenemia, ‘heavy’ spin, plasma supernatant, cryosupernatant, cryodepleted plasma, Food and Drug Administration, vitamin K-dependent factors, contact factors, TRUST guidelines, desmopressin, factor XIII deficiency, Kasabach-Merit phenomenon, transfusion-associated circulatory overload, transfusion related acute lung injury, transfusion reactions, enveloped viruses, hemostatic therapy, thromboelastography.


He L, Tronstad KJ, Maheshwari A. Mitochondrial dynamics during development. Newborn 2023; 2(1):19-44. DOI: 10.5005/jp-journals-11002-0053.

Abstract: Mitochondria are dynamic membrane-bound organelles in eukaryotic cells. These are important for the generation of chemical energy needed to power various cellular functions and also support metabolic, energetic, and epigenetic regulation in various cells. These organelles are also important for communication with the nucleus and other cellular structures, to maintain developmental sequences and somatic homeostasis, and for cellular adaptation to stress. Increasing information shows mitochondrial defects as an important cause of inherited disorders in different organ systems. In this article, we provide an extensive review of ontogeny, ultrastructural morphology, biogenesis, functional dynamics, important clinical manifestations of mitochondrial dysfunction, and possibilities for clinical intervention. 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.

Key scientific associationsnewborn, neonate, infant, ontogeny, outer membrane, intermembrane space, inner membrane, matrix, mitochondrial DNA, archezoan, endosymbiont, mitochondrion-related organelles, biogenesis, epigenetic, mitochondrial function, somatic homeostasis, cellular adaptation, mitochondrial dysfunction, oocyte, embryo, oxymonad, Monocercomonoides, numerical heterogeneity, cristae, Cryo-electron tomography, tubular network, filaments, dynamin-related GTPases, translocase of the outer mitochondrial membrane, topogenesis of mitochondrial outer membrane β-barrel proteins/sorting and assembly machinery, mitochondrial import complex, endoplasmic reticulum-mitochondria encounter structure, voltage-dependent anion channels, bax, bak, intermembrane space, cytochrome c, electrochemical membrane potential, IMM translocase, complex I, complex II, succinate: coenzyme Q oxidoreductase, complex III, coenzyme Q: cytochrome c oxidoreductase, complex IV, cytochrome c oxidase, ATP synthase, mitochondrial contact site, cristae organizing system, optic atrophy-1, F1F0 ATP synthase, aquaporin conduits, tricarboxylic acid, citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, fumarase, malate dehydrogenase; succinate dehydrogenase, archezoan, proto-mitochondrial endosymbiont, symbiogenesis, proteobacterium, mitochondrion-related organelles, hydrogenosomes, tricarboxylic acid cycle, electron transport chain, Clostridium, Trichomonas vaginalis, iron–sulfur (Fe–S) clusters , mitosomes, amoebozoons, transitional MROs, anaerobic ciliates, diatoms, Rickettsiales, Rickettsia, Ehrlichia, Anaplasma, Rickettsiaceae, Anaplasmataceae, HIMB59, Holosporaceae, SAR, Stramenopila, Alveolata, and Rhizaria, phylogenetic signal, long-branch attraction, sequence composition bias, first eukaryotic common ancestor, last eukaryotic common ancestor, superphylum Asgard, superphylums Planctomycetes, verrucomicrobia, Chlamydiae, domain archaea, Crenarchaeota, Thaumarchaeota, and Korarchaeota, syntrophic consortium model, endospore model, outside-in models, inside-out model, coat protein II, linker of nucleoskeleton and cytoskeleton (LINC), glycerol-3-phosphate lipids, autoreplication, translocase of the inner membrane, presequence translocase-associated motor, Hsp70, sorting and assembly machinery, PGC-1α, uncoupling protein 2, nuclear respiratory factor, δ-aminolevulinate synthase, fis-type proteins, Kleiber's power law, through tunnelling nanotubes and connexin 43 gap junctions, methionine-adenosyl transferase, histone demethylation , JMJ (jumonji, or the Jarid2) deamylase, sirtuins, FADH2, oogonia, urea cycle, carbamoyl phosphate synthetase I, ornithine transcarbamylase, mitochondrial respiratory chain, Leigh Syndrome, lethal infantile mitochondrial disease, lactic acidosis, MELAS syndrome, and Leber’s Hereditary Optic Neuropathy, mitochondrial leukoencephalopathy, cardiomyopathy, infantile leukodystrophy, Kearns-Sayre syndrome, mitochondrial chaperone BCS1 (BCS1L), Ubiquinol-Cytochrome C Reductase-Binding Protein (UQCRB), Ubiquinol-Cytochrome C Reductase Complex III Subunit VII (UQCRQ) and mitochondrially-encoded Cytochrome B (MTCYB), PAMP, DAMP, ubiquinone (Q)-cycle, necroptosis, phosphoglycerate mutase, receptor-interacting serine-threonine kinase, DNA polymerase γ, mitophagy, Parkin.


Singh S, Panghal A , Mane S, et al. Congenital Chikungunya Virus Infections. Newborn 2023; 2(1):45–59. DOI: 10.5005/jp-journals-11002-0054.

Abstract: Chikungunya virus (CHIKV) is an arthropod-borne ribonucleic acid (RNA) virus, classified in the genus alphavirus in the family Togaviridae. Perinatal/neonatal infections are rare, but some infants can develop fever, thrombocytopenia, lymphopenia, pigmentary changes, and a maculopapular rash. The neurocognitive outcome of some infants with vertically transmitted mother-to-child perinatal infections and CHIKV neonatal encephalopathy can be poor. The diagnosis of CHIKV infections can be confirmed by the detection of chikungunya viral RNA via real-time reverse-transcription polymerase chain reaction (RT-PCR) and/or specific immunoglobulin (Ig)M and IgG serology. Currently, no specific antiviral treatment(s) are available for CHIKV, and management is limited to supportive care by maintaining adequate intravascular volume by intravenous fluids and oral rehydration. Infants exposed in utero or during the perinatal period need to be monitored for adverse neurocognitive outcomes.

Key scientific associations:neonate, newborn, infant, chik sign, brownie nose, Aedes aegypti, Aedes albopictus, thrombocytopenia, vertical transmission, CHIKV encephalitis, hematocrit, platelets, fever, pregnant women, IgM anti-chikungunya virus antibodies, RT PCR, alphavirus, MV-CHIK vaccine, ECSA genotype, CHIKV-WH genotype, neurocognitive outcome.


Maheshwari A. Innate Immune Memory in Macrophages. Newborn 2023; 2 (1):60-79. DOI: 10.5005/jp-journals-11002-0058.

Abstract: Macrophages have been recognized as the primary mediators of innate immunity starting from embryonic/fetal development. Macrophage-mediated defenses may not be as antigen-specific as adaptive immunity, but increasing information suggests that these responses do strengthen with repeated immunological triggers. The concept of innate memory in macrophages has been described as “trained immunity” or “innate immune memory (IIM).” As currently understood, this cellular memory is rooted in epigenetic and metabolic reprogramming. The recognition of IIM may be particularly important in the fetus and the young neonate who are yet to develop protective levels of adaptive immunity, and could even be of preventive/therapeutic importance in many disorders. There may also be a possibility of therapeutic enhancement with targeted vaccination. This article presents a review of the properties, mechanisms, and possible clinical significance of macrophage-mediated IIM.

Key scientific associations: Fetus, newborn, neonate, development, epigenetics, innate immune memory, epigenetic reprogramming, trained immunity, sentinel cells, inflammation, adaptive immune cells, antimicrobial peptides, cytokines, trained immunity, phagocytosis, sensitized macrophages, embryonic development, pattern-recognition receptors, epigenetic memory, DNA methylation, histone modifications, non-coding RNAs, epigenetic tags, oocyte, tissue imprinting, epigenome, single-cell transcriptome, fate-mapping studies, promoters, enhancers, UMILILO, histone modifications, histone–histone interactions, histone–DNA interactions, H3K4me3, H3K4me1, activator protein 1, STAT, NF-kB, PU.1, H3K27ac, H3K9ac, H3K56ac, H4K91ac, nucleosome instability, phenotypic plasticity, pathogen-associated molecular pattern, damage-associated molecular patterns, Bacillus Calmette-Guerin, IL-12, memory T-cells, CD8αα, intestinal intraepithelial lymphocytes, HMGB1, porin, microbe-associated molecular patterns, inflammasomes, TLR5, ATF7, miR-155, miR-221, miR-222, SWI/SNF, β-glucan, mTOR, HIF-1α, histone acetyltransferases, histone deacetylases, chromatin, fumarate, succinic acid, α-ketoglutaric acid, glutamine, NLRP3, PIR-A, oxLDL, lipoprotein(a), MMP-2, MMP-9.


Verma A, Paul A, Tekleab AM, et al. Lung Ultrasound in Neonates: An Emerging Tool for Monitoring Critically-ill Infants. Newborn 2023; 2 (1): 80-90. DOI: 10.5005/jp-journals-11002-0057.  

Abstract: Context: Neonatal lung ultrasound is an emerging as a useful clinical tool for assessment of lung anatomy and management of various lung pathologies. In this review, we summarize normal lung ultrasound findings and specific features of various lung morbidities. Evidence Acquisition: A comprehensive literature search was conducted across multiple sources with relevant keywords and with anthe additional filter of the age group between 0-28 days. Findings: Apart from the description of normal newborn lungs, clinical and radiological features of a variety of  lung pathologies were evaluateddescribed and incorporated in the review. Bedside lung ultrasound has evolved to be an important point-of-care imaging modality that can help in day-to-day clinical decision-making. It can be used in differentiating respiratory distress syndrome from transient tachypnea of newborn, in the detection of pneumothorax, and in diagnosing pneumonia, pulmonary hemorrhage, and pleural effusion. Evidence supports the use of lung ultrasound scores to decide on the need for early rescue surfactant therapy with a high sensitivity and specificity. Lung ultrasound scores obtained during the first 1st and 2nd weeks after birth can help predict the likelihood of chronic lung disease/bronchopulmonary dysplasia. When Once validated, it could be a valuable tool infor guiding early intervention and evaluation of new treatments. Conclusions: Neonatal lung ultrasound will emergeis emerging as a vital monitoring tool in high-riskand critically-ill infants with lung diseasein the evaluation of a range of lung diseases. It will be valuable in early diagnosis, management, and prognosis of these patients. 

Key scientific associations: Neonate, newborn, infant, point-of-care lung ultrasound, respiratory distress syndrome, transient tachypnea of newborn, consolidation, atelectasis, pneumonia, pneumothorax, pulmonary hemorrhage, conventional lung ultrasound score (cLUS), modified lung ultrasound score, (mLUS), bronchopulmonary dysplasia.


Ethawi Y, Kasniya G, Al Baiti N, et al. Congenital Zika Virus Infections. Newborn 2023; 2(1):91-101. DOI: 10.5005/jp-journals-11002-0055.

Abstract: Zika virus (ZIKV) is an arthropod-borne flavivirus transmitted through bites of the Aedes mosquitoes. Infected mothers can vertically transmit Zika virus (ZV) to their fetuses, particularly during the first and second trimesters. Infections beginning during early gestation can cause congenital Zika virus syndrome (CZS), which may be marked by arrested development and/or altered healing in the nervous system. There can be microcephaly, craniosynostosis, intracranial calcifications, ventriculomegaly, low brain volume and/or cortical atrophy, and hypoplasia/altered myelination in the corpus callosum, cerebellum, and brainstem. There may also be altered development with polymicrogyria, pachygyria, and lissencephaly. Clinically, infants with CZS may show facial dysmorphism, pulmonary hypoplasia, altered growth and development, hypertonia, hyperreflexia, limb contractures, and arthrogryposis multiplex. Perinatal infections

Key scientific associations: newborn, neonate, infant, ZV, congenital Zika syndrome, CZS, Zika virus infection, ZVI, real-time reverse transcription-polymerase chain reaction, rRT-PCR, IgM, enzyme-linked immunosorbent assay, ELISA, microcephaly, ocular abnormalities, sensory neural hearing loss, SNHL, small gestational age, SGA, arthrogryposis, intracranial calcification, cerebrospinal fluid, CSF, plaque reduction neutralization test, PRNT, electroencephalogram, EEG, vertical transmission, head circumference, HC, length, weight, gestational age, GA, neuroimaging, head ultrasound, HUS, hearing test, cytomegalovirus, CMV, Computed tomography scan, CT scan, magnetic resonance imaging, MRI


Kaur P, Dudeja P. Pathophysiology of Enteropathogenic Escherichia coli-induced Diarrhea. Newborn 2023; 2(1):102–113. DOI: 10.5005/jp-journals-11002-0056.

Abstract: Enteropathogenic Escherichia coli (EPEC) are important diarrheal pathogens of infants and young children. Since the availability of molecular diagnosis methods, we now have new insights into the incidence and prevalence of these infections. Recent epidemiological studies indicate that atypical-EPEC (aEPEC) are seen more frequently than typical-EPEC (tEPEC) worldwide, including in both endemic diarrhea and diarrhea outbreaks. Therefore, it is important to further characterize the pathogenicity of these emerging strains. The virulence mechanisms and pathophysiology of the attaching and effacing lesion (A/E) and the type-three-secretion-system (T3SS) are complex but well-studied. A/E strains use their pool of locus of enterocyte effacement (LEE)-encoded and non-LEE-encoded effector proteins to subvert and modulate cellular and barrier properties of the host. However, the exact mechanisms of diarrhea in EPEC infection are not completely understood. From the clinical perspective, there is a need for fast, easy, and inexpensive diagnostic methods to define optimal treatment and prevention for children in endemic areas. In this article, we present a review of the classification of EPEC, epidemiology, pathogenesis of the disease caused by these bacteria, determinants of virulence, alterations in signaling, determinants of colonization vs. those of disease, and the limited information we have on the pathophysiology of EPEC-induced diarrhea. This article combines peer-reviewed evidence from our own studies and the results of an extensive literature search in the databases PubMed, EMBASE, and Scopus.

Key scientific associations: Epidemiology, attaching and effacing lesion (A/E), type III secretion system (T3SS), LEE pathogenicity island, tight junctions, ion transporters, EPEC, diarrhea, atypical-EPEC, Typical-EPEC, endemic diarrhea, diarrhea outbreaks, locus of enterocyte effacement (LEE), pool of locus of enterocyte effacement, LEE pathogenicity island (LPI), global regulator of LEE proteins, non-LEE-encoded effector proteins, determinants of virulence, localized adherence, electrolyte transport, loss of absorptive surface, summer diarrhea, classic EPEC, enteroaggregative E. coli, European, multicenter, prospective quarterly point-prevalence study of community-acquired diarrhea (EUCODI), Kauffmann system, somatic O, flagellar H, capsular K, flagella, Shiga toxin-producing E. coli (STEC), intimin, pEAF, operons, Type IV bundle-forming pilus, plasmid-encoded regulator, enterocyte effacement pathogenicity island, aggregative adherence nucleotide-binding proteins, BfpD, BfpF, filamentous actin, α-actinin, talin, ezrin, myosin-light chain, vasodilator-stimulated phosphoprotein (VASP), Wiskott–Aldrich Syndrome protein (WASP), actin-related protein 2/3, Ab1/Arg, Src, Tec,
Nck1, Nck2, actin nucleation-promoting factor, outer membrane needle, export apparatus, cytoplasmic sorting platform, mitochondrial dysfunction, filopodia, EPEC adherence factor, pMAR2, adhesins, brush border microvilli, cup and pedestal formations, glycocalyx, mucous pseudomembrane coating, translocated intimin receptor (tir), pseudopod-like structures, sodium-D-glucose cotransporter (SGLT-1), secretory immunoglobulin A, enteropathogens, Na + /H +  exchanger type 3 (NHE3), NleA, Map, Na+/H+  exchanger regulatory factor 2 (NHERF2), downregulated-in-adenoma (DRA/ SLC26A3), apical sodium-dependent bile acid transporter (ASBT), serotonin transporter (SERT), sodium-D-glucose transporter (SGLT1), occludin, tricellulin.

©2023 Global Newborn Society, "Every Baby Counts"

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