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JNB Oct-Dec 2022 V1 N4.tif

A composite PDF file containing all the articles in the fourth issue, 1 (4); October-December 2022 is provided here. 

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

Maheshwari A, Lui K, Motta M. Understanding the impact of Maternal Health on Neonatal Disease: A New Horizon. Newborn 2022; 1 (4):iv-vi. DOI: 10.5005/newborn-1-4-iv.


Srivastava A, Kaur S, Kamaluddeen M, Murthy P, Stritzke A, Al Awad E, Thomas S, Mohammad K, Soraisham A. Efficacy of Pharmacologic Therapy for Patent Ductus Arteriosus Closure in Preterm Small for Gestational Age Infants. Newborn 2022; 1 (4):327 - 332. DOI: 10.5005/jp-journals-11002-0048.



Objective: To determine the association between the degree of intrauterine growth restriction (IUGR) [defined by birth weight (BW) Z-score] and the efficacy of pharmacologic patent ductus arteriosus (PDA) closure and the rate of surgical PDA ligation in preterm neonates. Materials and methods: In this retrospective cohort study, we included neonates born below 30 weeks’ gestational age (GA), who received medical treatment for PDA between January 2010 and December 2018. Birth weight Z-scores were calculated using Olsen nomograms and classified into three categories: above −0.5; from −0.5 to −2.0; below−2. We compared responses to PDA treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and PDA ligations between these groups utilizing multivariable logistic regression analysis. Results: Of 769 neonates with PDA, 517 (67.2%) neonates received medical treatment for PDA. Of which, 323 (62.5%) had BW Z-score above −0.5, 154 (29.8%) had from −0.5 to −2.0., and 40 (7.7%) had below −2. The efficacy of the first course of NSAIDs for the PDA closure was not different among the three groups (51% vs 49% vs 50%). Multivariable logistic regression analysis showed there was no significant difference in PDA closure rate following the first course of NSAIDs between neonates with BW Z-score below −2 and those with BW Z-score above −0.5 [adjusted odds ratio (aOR): 0.68; 95% CI: 0.33–1.39] as well as those with BW Z-score from −0.5 to −2.0 (aOR: 0.89; 95% CI: 0.59–1.35). However, the odds of PDA ligation were significantly higher among neonates with BW Z-scores below −2 (aOR: 2.67, 95% CI: 1.12–6.34) but not among neonates with Z-scores from −0.5 to −2.0 (aOR: 1.41; 95% CI: 0.84–2.39), as compared to those with BW Z-scores above –0.5.

Conclusion: We observed a similar rate of PDA closure following the first course of NSAIDs between appropriately grown and growth-restricted neonates. However, severe growth restriction (BW Z-score below −2) is associated with higher rates of PDA ligation as compared to normally grown infants.

Key scientific associations: Ibuprofen, indomethacin, intrauterine growth restriction, patent ductus arteriosus, prematurity, pharmacologic PDA closure, surgical PDA ligation, non-steroidal anti-inflammatory drugs, multivariable logistic regression analysis, indomethacin, prostaglandins, hemodynamically-significant PDA, trans-ductal diameter, peak systolic velocity, left atrium to aortic ratio, LA: Ao, absent or reversed diastolic flow, z-scores, SNAP-II, Prostaglandin E2, adenosine monophosphate, protein kinase A, G protein–coupled receptors.


Mantry H, Maheshwari A. Quantum Cryptography for Securing Personal Health Information in Hospitals. Newborn 2022; 1 (4):333 - 339. DOI: 10.5005/jp-journals-11002-0043.

Abstract: Healthcare systems widely use information technology (IT) for system authentication (digital signatures), web surfing, e-mails, instant messaging, protecting data at rest, Voice over Internet Protocol (VoIP) telephony, and cellular telephony. To protect patient identification and healthcare information, cryptographic systems are widely used to secure these data from malicious third parties (adversaries). In our healthcare systems, we have had reasonable success in the efficient storage of the information of our patients and their families, in its timely retrieval, and in ensuring its safety from adversaries. However, the data are increasing rapidly and our current computational systems could be inadequate in the not-so-distant future. In this context, there is a need for novel solutions. One possibility can be seen in quantum computing (QC) algorithms/devices that can provide elegant solutions based on subatomic interactions. In this review, we have summarized current information on the need, current options, and future possibilities for the use of QC algorithms/devices in large data systems such as healthcare. This article combines peer-reviewed evidence from our own clinical studies with the results of an extensive literature search in the databases PubMed, EMBASE, and Scopus.

Key scientific associations: Newborn, neonate, baby, infant, healthcare systems, information technology, system authentication, digital signatures, web surfing, e-mails, instant messaging, voice over internet protocol (VoIP) telephony, cellular telephony, healthcare information, cryptographic systems, adversaries, secure hash algorithm,  triple data encryption algorithm system, advanced encryption standard, message-digest, RSA, personal health information, quantum computing, subatomic interactions, digital semiconductor processors, interface busses, QC algorithm, decryption, semiconductor, probabilities, certainties, quantum computing, electronic medical records, continuous monitoring, telehealth, at-home testing devices, computers, cloud, emails, servers, databases, cyberattacks, Health Insurance,  Portability and Accountability Act, WannaCry malware attacks, British National Health Service, credit card information, social security numbers, US Department of Health and Human Services, mother-infant units, NICUs, cryptography, encrypting, cipher, decrypt, key, private/symmetric key cryptography, public key cryptography, hacking, Diffie-Hellman key exchange protocol, Rivest-Shamir-Adleman, Elliptic Curve Cryptography, public key cryptosystems, advanced encryption standard, data encryption standard, RSA encryption systems, prime numbers, trapdoor function, elliptic curve cryptography, quantum computing, transistors, ket, Dirac notation, superposition, healthcare system, information technology, system authentication, digital signature, web surfing, tensor, quantum entanglement, TensorFlow quantum, hybrid quantum-classical ML models, quantum entanglement, position, momentum, spin, polarization, measurement problem, Schrödinger equation, quantum-mechanical system, linear superposition, no-cloning theorem, quantum algorithm, Shor’s algorithm, Grover’s algorithm, modular arithmetic, superposition, entanglement, interference, Deutsch-Jozsa, Bernstein-Vazirani, Simon, quantum Fourier transform, quantum phase estimation, quantum counting, quantum walk search, dense coding, quantum key distribution, BB84 Protocol, E91 Protocol, National Institute of Standards and Technology, cryptographic suite for algebraic lattices (CRYSTALS), FALCON, SPHINCS+, CRYSTALS-Kyber, lattice cryptography, multivariate cryptography, code-based cryptography, supersingular isogeny key exchange protocol, and symmetric key systems like AES and SNOW- 3G, transmons, superconductivity traps, QKD network.


Maheshwari A. The Phylogeny, Ontogeny, and Organ-specific Differentiation of Macrophages in the Developing Intestine. Newborn 2022; 1 (4):340-355. DOI: 10.5005/jp-journals-11002-0044. Available in PubMed.  

Abstract: Macrophages are large highly motile phagocytic leukocytes that appear early during embryonic development and have been conserved during evolution. The developmental roles of macrophages were first described nearly a century ago, at about the time these cells were being identified as central effectors in phagocytosis and elimination of microbes. Since then, we have made considerable progress in understanding the development of various subsets of macrophages and the diverse roles these cells play in both physiology and disease. This article reviews the phylogeny and the ontogeny of macrophages with a particular focus on the gastrointestinal tract, and the role of these mucosal macrophages in immune surveillance, innate immunity, homeostasis, tissue remodeling, angiogenesis, and repair of damaged tissues. We also discuss the importance of these macrophages in the inflammatory changes in neonatal necrotizing enterocolitis (NEC). This article presents a combination of our own peer-reviewed clinical and preclinical studies, with an extensive review of the literature using the databases PubMed, EMBASE, and Scopus. 

Key scientific associations: phagocytic leukocytes, immune surveillance, innate immunity, homeostasis, tissue remodeling, angiogenesis, repair of damaged tissues, cytoplasm-to-nucleus ratio, lineage-committed bone marrow precursors, circulating monocytes, resident macrophages, dendritic cells, Trichomonas vaginalis, amebocytes, celomocytes, hemocytes, scavenger receptor cysteine-rich domains, diploblastic animals, pore-forming proteins, macrophage-expressed gene 1 protein, triploblasts, mesoglea, Protostomia, Deuterostomia, triploblastic prostomes, celomatic animals, mesenteric layer, fruit flies, Annelids, Toll-like receptor, deuterostome, chordates, Chordata, Echinodermata, zebrafish, complement Clq, G-protein-coupled receptor 35, amphibian, CXC ligand 12, subepithelial lymphoid aggregates, factor c-Myb, erythro-myeloid progenitors, aorta-gonad-mesonephros, hematopoietic stem cells, common myeloid progenitors, dorsal aorta, Kupffer cells, common myeloid progenitors, granulocyte-monocyte precursors, common monocyte and DC precursors (MDP), pre-monocytes, committed monocyte progenitors, monocytes, committed monocytes, classically-activated M1, alternatively-activated M2, CX3CR1, CD204,mannose receptor, plasticity, clonal expansion, chemerin, lamina propria macrophages, submucosal macrophages, muscularis macrophages, adrenergic/arginase 1/polyamines axis, serosal macrophages, nuclear factor kappa-B kinase subunit β, smad7, H2A-H2B dimer, Peyer’s patches, hemoglobin-haptoglobin complex, T-cell membrane protein, Wiskott-Aldrich Syndrome protein, dedicator of cytokinesis, Dectin-1.


Huseynova RA. Effect of Ursodeoxycholic Acid in Unconjugated Hyperbilirubinemia in Term Neonates Treated with Phototherapy: A Systematic Review. Newborn 2022; 1 (4):356-367. DOI: 110.5005/jp-journals-11002-0046.


Background: Neonatal hyperbilirubinemia is a common clinical condition worldwide. Phototherapy (PT) is the standard intervention for hyperbilirubinemia; however, it may have side effects. It has been suggested that the implementation of adjuvant therapy including ursodeoxycholic acid (UDCA), for example, may decrease the duration of PT.

Objectives: To determine the efficacy and safety of UDCA in addition to PT in term neonates with unconjugated hyperbilirubinemia (UH) vs PT alone.

Methods: A systemic review was undertaken using the following databases: PubMed, Medline, Cochrane database, Scopus, Google Scholar, and Randomized controlled trials (RCTs) assessing the efficacy and safety of UDCA combined with PT on the total serum bilirubin (TSB) and duration of PT were included. The data quality assessment was carried out. Results: Low–moderate quality evidence from seven RCTs reported significantly lower TSB levels in the UDCA group compared to the control group after 12, 24, 48, and 72 hours of treatment with a mean difference (MD) of –2.23 mg/dL (95% CI: from −2.49 to −1.96); −1.59 mg/dL (95% CI: from −1.83 to −1.35); −1.03 mg/dL (95% CI: from −1.27 to −0.79); and −1.32 mg/dL (95% CI: from −1.63 to −1.01), respectively, with heterogeneity of studies I2 = 92% (p < 0.00001). In addition, three studies observed that UDCA significantly decreased the duration of PT with MD −19.14 hours (95% CI: from −20.70 to −17.59) with heterogeneity I2 = 91% (p < 0.00001). None of the studies reported any significant adverse effects of UDCA.

Conclusion: Ursodeoxycholic acid combined with PT in the treatment of UH significantly reduces the TSB and duration of PT without significant risk of adverse events. However, limited and low–moderate quality evidence exists to support the routine use of UDCA in neonates. We discuss the limitations of the review results for clinical practice.

Key scientific associationshyperbilirubinemia, physiological jaundice, phototherapy, UDCA ursodeoxycholic acid, neonates, systematic review, fetal erythrocytes, hepatic excretory capacity, ligandin, glucuronyl transferase, hemolytic disease, sepsis, polycythemia, extravasation of blood, metabolic disorders, water-soluble bilirubin photoproducts, kernicterus, γ-glutamyl transpeptidase, Boolean operators, Quality of evidence, GRADE tool, enterohepatic recirculation, cholangiocytes, hydrophobic bile acids.


Anand P, Singh S, Schelonka RL, Tekleab AM, Upadhyay A. Hepatitis B Infections in Neonates. Newborn 2022; 1 (4):368-375. DOI: 10.5005/jp-journals-11002-0049.

Abstract: Hepatitis B infections are estimated to affect more than 2 billion people worldwide. The overall prevalence of HBsAg positivity in plasma is reported to be 3.5%, but it varies depending on the geographic area. Mother-to-child infection is the predominant mode of transmission in high-prevalence areas. In exposed infants, universal hepatitis B vaccination and the administration of hepatitis B immunoglobulin (HBIg) within 12 hours following the birth can reduce the risk of perinatal infection. The rates of progression to chronic hepatitis B infection depend on the age of infection and are the highest in perinatally acquired infections, thus underscoring the importance of measures to reduce transmission. Timely identification and treatment of the affected pregnant women and immunoprophylaxis of newborn infants are of paramount importance to reduce the burden of chronic infection..

Key scientific associations: Hepatitis B, neonate, epidemiology, maternal-to-neonate transmission, prevention, maternal Hepatitis B infection, tenofovir prophylaxis, Hepadenaviridae, HBeAg, transplacental route, placental barrier, villous capillary endothelial cells, trophoblasts, maternal viral load, syphilis, congenital malaria, congenital dengue, congenital chikungunya, inborn errors of metabolism presenting with hepatic failure, immune tolerant phase, interferon, nucleoside analogues, single-antigen vaccines.


Rahman MM, Khatun S, Kabir N, Khanam W, Maheshwari A, Shahidullah M. Establishment of the First Religiously-compliant Human Milk Bank in Bangladesh. Newborn 2022; 1 (4):376-383. DOI: 10.5005/jp-journals-11002-0047.

Abstract: Human milk banks (HMBs) collect, screen, process, and dispense donated human milk (HM). There are more than 500 large HMBs in the world but only a few are functioning in Muslim countries, and that too on a limited scale. Human milk banks that are similar to those in the Western countries have been difficult to establish in Muslim countries as Islamic laws do not allow the consumption of unidentified donated milk from multiple donors. Human milk is known to be important for nutrition in premature and critically ill infants, and so there is a well-recognized need to develop religiously compliant and conditionally identified HMBs in Muslim countries. In these milk banks, every mother's milk is processed and stored separately, and the milk provided by one mother can be provided to an infant from a different family only after appropriately counseling both families about the Islamic laws of prohibition of future marriages between milk siblings. Documents related to these issues are provided to both families and data need to be maintained for future reference. In this article, we recount the educational, financial, and infrastructural challenges that we faced in establishing religiously-compliant HMB in Bangladesh. There is already a noticeable reduction in infant mortality in our region.

Key scientific associations: Human milk bank, conditionally-identified milk bank, milk siblings, breastmilk, newborns, premature, appropriate for gestational age, large for gestational age, small for gestational age, Muslim countries, Islamic law, unidentified donated milk, religiously-complaint milk bank, conditionally-identified milk bank, milk siblings, World Health Organization, infant feeding, donor milk, mother’s own milk, MOM, donated human milk, pasteurized donor human milk, Islamic tradition, feeding intolerance, Pasteurizer, laminar air flow machine, hot air oven, breast pump, data-entry system, Islamic foundation for religious clarification, Halal certificate, Surah An-Nisa, Surah-4, Al-Quran, Holy Quran, triglycerides, microbiological screening, disbursal, labeling and record-keeping, traceability.


Maheshwari A. Fats in Human Milk: 2022 Updates on Chemical Composition. Newborn 2022; 1 (4):384-396. DOI: 10.5005/jp-journals-11002-0050.

Abstract: Human milk (HM) feedings are important for all newborn infants. Healthy term infants grow well with the mother's own milk (MOM), be it in direct breastfeeding or when fed expressed breastmilk. Premature and ill infants being treated/monitored in neonatal intensive care units (NICUs) also recover better when fed with HM diets, which can include MOM, donor milk (DM), or a combination of both. In terms of chemical composition, it contains 3–5% fat, 0.8–0.9% protein, 6.9–7.2% carbohydrates (calculated as lactose), and 0.2% mineral constituents. In this review, we present the latest information on HM fats, including triglycerides, phospholipids, triglycerides, cholesterol, glycoproteins, and enzymes. This article is intended to initiate a series of periodic updates on the scientific information available on HM fats. It contains some of our own research findings with an extensive review of the literature. To avoid bias in the identification of studies, keywords were short-listed a priori from anecdotal experience and from PubMed's Medical Subject Heading (MeSH) thesaurus. We then searched the databases PubMed, EMBASE, and Science Direct..

Key scientific associations: infants, neonate, newborn, mother’s own milk, premature, neonatal intensive care unit, donor milk, triglycerides, phospholipids, triglycerides, cholesterol, glycoproteins, enzymes, bovine fortifiers, essential fatty acids, HM-derived fortifiers, donor milk, infant formula, Baby-Friendly Hospital Initiative, triacylglycerols, cholesterol esters, phospholipids, glycerol, stereospecific numbering, long-chain polyunsaturated fatty acids, palmitic acid, unsaturated fatty acids, monoacylglycerols, oleic, linoleic, acetyl-CoA, malonyl-CoA, acyl thioester-hydrolase, long chain FAs, glycerol-3-phosphate, biomimetic infant formula, lingual lipase, bile acids, pancreatic lipase, medium-chain triglycerides, oleic, palmitic, linoleic, myristic, stearic acid, α-linolenic acid, arachidonic acid, docosa­hexaenoic acid, capric acid, arachidic, behenic acid, caprylic, capric acid, lauric acid, dodecanoic acid, myristic acid, tetradecanoic acid, palmitoleic acid, European Food Safety Authority, docosahexaenoic acid, synaptic membrane, chylomicron, dihomo-γ-linolenic acid, Cochrane review, carnitine.


Padhi BK, Manna S, Pallepogula DR, Kumar J, Joshi B, Sah R, Aggarwal AK, Maheshwari A. Prevalence of Gram-negative Bacteria in Maternal Cervical Secretions: A Systematic Review and Meta-analysis. Newborn 2022; 1 (4):397-407. DOI: 10.5005/jp-journals-11002-0051.

Abstract: In neonates, early-onset sepsis (EOS) occurring within 72 hours after birth is an important cause of mortality worldwide. Emerging data show that EOS may occur more frequently in tropical and peri-equatorial regions with more gram-negative bacteria than in the Western countries. This systematic review aimed to estimate the prevalence of gram-negative bacteria in the maternal genital tract during the peripartum period.

Materials and methods: We explored the primary research studies that reported the presence of gram-negative bacteria in the maternal genital tract using the software STATA, version 17.1. Five databases, PubMed, Embase, Scopus, Web of Science, and ProQuest were searched until October 2022. Data were analyzed using random-effects meta-analyses to determine the prevalence of gram-negative bacteria in the maternal genital tract.

Results: Fifteen studies qualified for analysis by our predetermined inclusion criteria. The overall prevalence of gram-negative bacteria in cervical secretions was 23.20% (95% CI [confidence interval]: 11.77–37.08, I2: 99.79%). Escherichia coli (15.3%) and Acinetobacter (0.36%) species reported the highest and lowest prevalent bacteria, respectively. The prevalence of other gram-negative species was Klebsiella pneumoniae (0.47%), Pseudomonas (2.81%), Enterobacter (3.33%), Alcaligenes faecalis (1.32%), Proteus vulgaris (10.0%), and Providencia alcalifaciens (10%). Most of the studies were from tropical countries, and there was a positive linear relationship between the studies. Conclusion: Gram-negative colonization of the maternal cervical-vaginal tract may be more frequent than previously recognized in tropical/peri-equatorial regions of the world. Early identification of these bacterial pathogens may help in timely evaluation and treatment of these infants.

Key scientific associationsnewborn, neonate, premature, Gram-negative sepsis, early-onset sepsis, prolonged hospitalization, critical care devices, central lines and assisted ventilation, intestinal disorders, necrotizing enterocolitis, tropical regions, peri-equatorial regions, Gram-negative pathogens, E. coli, Acinetobacter, Klebsiella pneumoniae, Pseudomonas, Enterobacter, Alkaligenes faecalis, Proteus vulgaris, Providencia alkalifaciens, Group B Streptococcus, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus, Enterobacteria, Edwardsiella, urogenital tract infection, premature rupture of membranes, colonization, random-effects model, effect sizes, publication bias, funnel plot, bubble graph, hematogenous infections, plasmids, acute suppurative placentitis, American Society of Infectious Diseases, PRISMA flow chart.

©2024 Global Newborn Society, "Every Baby Counts"

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