Maheshwari A, Lui K, Motta M. Healthcare Bundles are Potentially Important in Neonatal Care as Many Disorders are Temporally Clustered. Newborn 2024; 3(3):iv-ix. DOI: 10.5005/newborn-3-3-iv.

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The LAYA* Group of the Global Newborn Society. A Care-bundle to Prevent Germinal Matrix–Intraventricular Hemorrhage in Neonates. Newborn 2024; 3(3):157-179. DOI: 10.5005/jp-journals-11002-0096. *Looking At Your practices in Application.

 

Abstract: Germinal matrix-intraventricular hemorrhages (GM-IVHs) can be seen in up to 25–30% of premature infants. These are associated with a major psychological, social, and financial challenge for care-providers and families caring for premature infants all over the world. The severity is usually classified based on the location and volume vis-à-vis that of the cerebral ventricles, including (A) Grade I GM-IVHs localized in the germinal matrix; (B and C) Grade II and III hemorrhages occupying less than and more than 50% of the ventricular cavities, respectively; and (D) Grade IV IVHs that extend into the surrounding parenchyma with/without a periventricular hemorrhagic infarction (PVH). Germinal matrix-intraventricular hemorrhages have been associated with impaired neurodevelopment (17.5%), static physical disabilities in cerebral palsy (7–63%), deafness (8.6%), and blindness (2.2%). Considering the complex etiopathogenesis of GM-IVH and the fact that most of these events occur within a temporally-delimited period of the first 72 hours after birth, there is increasing interest in the structured application of 3–5 well-accepted preventive measures as a quality improvement (QI) “care bundle” during the high-risk period. In this article, we have described the evidence on which our GM-IVH bundle is based. We have carefully evaluated antenatal factors such as the history of having received steroids and magnesium sulfate, perinatal measures such as delayed cord clamping, management of thrombocytopenia and/or coagulopathy, and postnatal measures such as maintaining a midline head position, cautious endotracheal suctioning and blood withdrawals, and avoidance of routine flushing of intravenous and arterial lines. Based on the strongest evidence and practice consensus, we have adopted a 4-point bundle to prevent GM-IVH in premature infants: (A) Appropriate neonatal resuscitation with, if possible, delayed cord clamping; (B) Golden-hour care; (C) Gentle care of outborn infants including safe transport and avoiding hemodynamic instability; and (D) if needed, management of perinatal thrombocytopenia and coagulopathy. In the next 3–5 years, we will report compliance and changes in the incidence/severity of GM-IVH at our centers.

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Key scientific associations: Newborn, neonate, preterm, quality improvement, germinal matrix, periventricular hemorrhage, Institute of Health Care Improvement, GM-IVH Care-bundle, cerebral palsy, blindness, golden hour, antenatal corticosteroids, delayed cord clamping, implementation science, tocolytics, preterm premature rupture of membranes (PPROM), periventricular leukomalacia, periventricular hemorrhagic infarction, neurodevelopment, thrombocytopenia, coagulopathy, midline head position, cautious endotracheal suctioning, outborn infants, safe transport, compliance, premature cerebral vasculature, cerebral blood flow, ventricular distention, periventricular echodense area, glial precursor cells, angiogenesis, pericytes, immature basal lamina, astrocyte end-feet coverage, glial fibrillary acidic protein, epileptiform seizures, cognitive delays, vibrations, protocolization, PPROM, sexually-transmitted diseases, chorioamnionitis, erythromycin, clarithromycin, ceftriaxone, metronidazole, matrix metalloproteinase-8, American College of Obstetricians and Gynecologists, indomethacin, EPIPAGE-2, atosiban, oxytocin receptor antagonist, calcium channel blocker, APOSTEL-III trial, Ritodrine, German Neonatal Network, Cochrane review analysis, foramen ovale, early cord clamping, monochorionic twins, intrauterine growth restriction, hydrops fetalis, hypothermia, hypoglycemia, polyethylene bags, snap-open access port covers, air-boost on transport incubators, gel-filled thermostable mattresses, infrared thermometers, infrared thermography, International Electrotechnical Commission, Ground Ambulance Transport, noise, newborn emergency transport service (NETS) teams, real-time NIRS monitoring, sleep-wake states, REM sleep, Intubation-Surfactant delivery-and Extubation (InSurE), LISA (Less Invasive Surfactant Administration), SALSA (Surfactant Administration through the Laryngeal or Supraglottic Airway), blenders, permissive hypercapnia, cerebrovascular autoregulation, pain, accentuated neuronal excitation, apoptosis, subcortical grey matter maturation, pain-induced prefrontal activity, Kangaroo mother care, oral sucrose gel, fetal/neonatal alloimmune thrombocytopenia, human platelet antigens, HLA, vitamin K reductase, apolipoprotein, collagen 4A1, PlaNeT-2 trial, melatonin, caffeine, azithromycin, anakinra, haptoglobin, oligodendrocytes, implementation science.

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Badarch J, Kumar G, Enkhbayar B, Turbat T, Sereenendorj T, et al. Down Syndrome is the Leading Indication for Late-stage Termination of Pregnancy in Mongolia. Newborn 2024; 3(3):180-189. DOI: 10.5005/jp-journals-11002-0099. 

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Abstract:

Background: Prenatal sonograms frequently show congenital anomalies in fetuses. As expected, families receiving information about severe or multi-system anomalies experience ceaseless distress and may request for termination of the pregnancy. This study was designed to identify the most frequent indications for termination of pregnancy for fetal anomalies (TOPFAs). These data can help in early detection, which can then facilitate informed decisions either for safe terminations or for well-timed fetal procedures for rehabilitation. This information is also important for appropriate genetic testing and assessment of the risk of recurrence in later pregnancies. 

Objective: To investigate the frequency and epidemiological profile of various fetal abnormalities that have evoked requests for late termination of pregnancy in Mongolia. Materials and methods: This cross-sectional observational study was conducted in a cohort of 45,095 pregnancies. Of these, 156 were terminated because of fetal anomalies. Data pertaining to fetal/congenital anomalies were collected after informed consent from families and compared with 312 healthy controls to evaluate associated maternal risk factors. 

Results: In this cohort, 34.5 in 10,000 pregnancies were terminated because of fetal anomalies during the study period 2017–2019. A total of 156 terminations were related to congenital anomalies. Down syndrome (DS) was the most frequent reason (25%). The other leading reasons were multiple congenital anomalies (16%), cleft lip/palate (10.9%), and anomalies of the central nervous system (9.6%) or the musculoskeletal system (9.6%). Maternal age >35 years, higher education, less spacing between successive pregnancies, and previous history of abortion(s) were associated with a higher likelihood of birth defects. 

Conclusion: Down syndrome is the leading indication for late-stage TOPFAs in Mongolia. Multi-system congenital anomalies, clefts, and anomalies of the central nervous system and musculoskeletal system were other reasons that led to requests for termination of pregnancy.

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Key scientific associations: Birth defect, Congenital anomalies, Termination of Pregnancy for Fetal Anomaly, TOPFA, Chromosomal anomalies, Down Syndrome, Global burden of disease study, maternal age, newborn, risk factors, chromosomal defects, organ system defects, temporal trends, intrauterine growth restriction, Global Burden of Disease study, environmental contaminants, radiation, International Classification of Diseases, 63rd World Health Assembly, socio-demographic information, mother-baby dyads, chromosomal abnormalities, cleft lip and palate, migration defects, phocomelia, Migration defect, Hydrocephalous, Cerebellar agenesis, brachydactyly, acromesomelic dysplasia, polycystic kidney, megabladder, kidney cyst, kidney dysplasia, ventricular septal defect, malposition of aorta, microtia, microphthalmia, hypospadias, consanguinity, aorta malposition, Cu/Zn-superoxide dismutase, amyloid precursor protein, World Down Syndrome Day, EUROCAT, International Classification of Diseases.

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Hoyos AB, Vasquez-Hoyos P. Safety of Full Enteral Feedings Initiated Soon after Birth Instead of Parenteral Fluids in Clinically Stable 30–34 Weeks Gestation Premature Infants. Newborn 2024; 3(3):83–89. DOI: 10.5005/jp-journals-11002-0101. 

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Abstract:

Background: Many neonatal intensive care units use feeding protocols where infants born at 30–34 weeks’ gestation are maintained exclusively on parenteral fluids for variable periods without enteral feedings, until there is confirmed hemodynamic stability without any doubt. In addition to the pain and discomfort, intravenous infusions are associated with an increased risk of hospital-acquired infections, which makes it an undesirable practice if not essential. 

Objective: In this quality improvement (QI) effort, we tested the safety and efficacy of enteral feedings starting within the first 2 hours after birth in infants born at 30–34 weeks’ gestation. 

Materials and methods: Instead of intravenous fluids, we initiated fluid management in infants born at 30–34 weeks’ gestation using oral/nasogastric milk feedings at 70–80 mL/kg/day divided every 3 hours, with 5 mL increments every 12–24 hours until 200 mL/kg/day was achieved. We compared the utilization of parenteral fluids, the incidence of infection, and growth before and after initiation of this new feeding policy. 

Results: In our experience, these infants tolerated and utilized enteral feedings well with stable growth and biochemical parameters. They also tolerated daily volume increments in the enteral feedings. We did not find any hypoglycemic events as the first enteral feeding was administered within 2 hours after birth. The enterally fed group showed a similar safety profile with similar weight at discharge and weight Z-scores. We report that infants born as early as 30 weeks gestation can safely tolerate ab initio full enteral feedings. 

Conclusion: Enteral feedings beginning within 2 hours after birth are a safe and efficacious strategy for fluid management in premature infants born at 30–34 weeks gestation. Routine use of parenteral fluids is not necessary in the initial management of these infants.

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Key scientific associations: newborn, neonate, parenteral fluids, late premature infants, hospital-acquired infections, umbilical lines, central venous lines, early oral feeds, nutrition, Z-score, nil per os, NPO, enteral nutrition, necrotizing enterocolitis, neonatal sepsis, mortality, milk fortifiers, demographics, chorioamnionitis, congenital anomalies, hypoglycemia, intestinal perforation, neuromotor integrity. 

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Mohammadabadi T, Kumar G. Camel Milk as a Source of Nutrients and Immunogens for Infants. Newborn 2024; 3(3):195-205. DOI: 10.5005/jp-journals-11002-0106. 

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Abstract: Camel milk stands as a vital resource for infants in arid and semi-arid regions. Despite representing a modest 0.36% of global milk production, its nutritional composition is remarkable. With 3.4% protein, 4.4% lactose, and 3.5% fat, it offers a unique blend of nutrients that is comprised of higher levels of essential vitamins and minerals compared with cow's milk. Notably, its vitamin C content surpasses that of cow's milk by a significant margin. This nutritional powerhouse is particularly beneficial for individuals allergic to cow's milk, as it lacks β-lactoglobulin. Beyond its nutritional profile, camel milk contains nanobodies that stimulate immune responses, unsaturated fatty acids for heart health, and insulin-like proteins that are stomach-friendly. Moreover, its probiotic bacteria aid in reducing cholesterol absorption and possess antibacterial properties, further enhancing its health benefits. In essence, camel milk transcends its role as mere sustenance, emerging as a potent superfood with the potential to address various health complications.

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Key scientific associations: Camel milk, composition, superfood, health, arid, semi-arid, food security, vitamin C, atopy, nanobodies, insulin-like proteins, probiotic, prebiotic, cholesterol, 1-humped dromedary, 2-humped Bactrian, wild Bactrian camels, dairy industry, Pakistani camels, Kazakhstan camels, micelles, Camelidae, llamas, alpacas, vicuñas, guanacos, lysine, glycine, threonine, valine, insulin-like protein, IgG sub-classes, cysteine, disulphide, beta-casein, alpha1-casein, kappa-casein, lysozyme, micelles, efficiency, efficacy, effectiveness, hepatitis C, Foot and Mouth virus, Rift Valley fever virus, Rinderpest virus, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, sphingomyelin, fatty acids, plasmalogens, minerals, Bifidobacteria, Oligosaccharides, N-acetyl glucose aminidase, lysozyme, lactoferrin, lactoperoxidase, peptidoglycan, sialyl oligosaccharides, nutraceutical 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid, angiotensin-converting-enzyme, glutathione, superoxide dismutase, glutathione peroxidase, autism-spectrum disorder, Childhood Autism Rating Scale.

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Garegrat R, Chetan C, Puri R, Chandrakala BS, Nagpal R, et al. Cranial Ultrasound as an Imaging Modality in Neonatal Sepsis to Determine Involvement of the Central Nervous System. Newborn 2024; 3(3):206-218. DOI: 10.5005/jp-journals-11002-0103. 

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Abstract:

Background: Globally, neonatal sepsis continues to be a significant cause of neonatal morbidity and mortality. Bedside point-of-care cranial ultrasound (POCUS) can help determine whether the central nervous system (CNS) is affected. It can help evaluate meningitis, brain abscess, changes in the spinal cord, and alterations in cerebral blood flow; it can even provide some clues for early identification of fungal and viral infections. This information can aid in appropriate management. 

Methods: A comprehensive literature search was conducted to review hallmark POCUS findings in neonatal sepsis with CNS involvement. Further inputs were gathered on understanding the role of these findings in prognosticating and defining the duration of management. 

Results: The review focused on the classical findings seen on cranial ultrasound, with meningitis in the cerebrum and spinal cord. The complications of meningitis, like ventriculitis, cerebral abscess, and cerebral thrombosis along with other fungal and perinatal infections with their ultrasound findings have been highlighted in this review article. 

Conclusion: POCUS is a useful bedside screening tool for the diagnosis and management of neonates with meningitis and its complications. Its ease of usage, with safety, and a lesser turnaround time make ultrasound superior to other imaging techniques in neonatal infections.

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Key scientific associations: neonates, sepsis, Point-of-care ultrasound, POCUS, meningitis, brain abscess, central nervous system, fungal infections, viral infections, ventriculitis, cerebral abscess, cerebral thrombosis, ionizing radiation, sedation, cerebral calcifications, ischemic lesions,  hematomas, late-onset neonatal sepsis, hydrocephalus, severity-of-illness, neurodevelopmental outcomes, anterior fontanel, acoustic window, Group B streptococci, Gram-negative bacilli, Listeria monocytogenes, Proteus, Citrobacter, Streptococcus, Serratia, Neisseria meningitis, Candida albicans, Candida parapsilosis, herpes simplex, parvovirus, Zika virus, rotavirus, pustular cavity, meningeal thickening, brain sulci, cerebral gyri, sulci, gyral surface, sagittal sinus, perforating vessels, extra-axial fluid collections, reactive effusions, chinking of ventricles, empyema, cerebral thrombosis, ependymitis, choroid plexitis, arachnoiditis, fibroglial elements, non-communicating hydrocephalus, ventriculomegaly, ex vacuo ventriculomegaly, ventricular index, anterior horn width, thalamo-occipital distance, occipital horn, fibrous septae, intraventricular compartmentalization, intraventricular cysts, obstructive hydrocephalus, cisternal structures, resistive index, infarction, cerebritis, vertebral arch, spinous processes, pulsatility of arterial blood flow, granulomas, micro-abscesses.

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Singh S, Frydrysiak-Brzozowska A, Ben Ayad AE, Khasanova SS, Jeremias Bordon J, et al. A Primer on Epigenetic Changes: The More We Know, the More We Find in Fetuses and Infants. Newborn 2024; 3(3):219-232. DOI: 10.5005/jp-journals-11002-0104.

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Abstract: Epigenetics is the study of heritable traits that happen without changes to the DNA sequence. The Greek prefix epi- implies features that modify the traditional genetic mechanisms of inheritance. Increasing information underscores the importance of epigenetic changes during the fetal period and infancy. The most frequently seen epigenetic changes are mediated via DNA methylation, changes in gene expression due to non-coding RNAs, and post-translational modifications of histone proteins. DNA methylation can be confirmed using methods such as bisulfite treatment, enzyme sensitivity assays, and antibody specificity-based techniques. Histone modifications are typically detected through antibody recognition. Chromatin immunoprecipitation (ChIP) is an antibody-based technology to selectively enrich specific DNA-binding proteins along with their DNA targets. Since epigenetic alterations are often reversible, modifying epigenetic marks contributing to disease development may provide an approach to designing new therapies. Gene hypermethylation and histone hypoacetylation are attractive targets for the treatment of epigenetic diseases because these epigenetic alterations are reversible. The first 1000 days of life, from conception through infancy, comprise the most-likely time-period for environmental exposures and nutrition to exert beneficial/potentially harmful epigenetic effects. During this period, a typical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic diseases. Epigenetics also plays a role in the developmental origins of adult metabolic diseases.

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Key scientific associations: neonate, newborn, infant, DNA methylation, RNA silencing, post translational modification, miRNA, histones, genomic imprinting, lncRNA, ncRNA, heritable, chemical tags, gene expression, non-coding RNA, post-translational modifications, histone, bisulfite, enzyme sensitivity, and antibody specificity, chromatin immunoprecipitation, metabolic reprogramming, extrinsic factors, allergens, viruses, pollutants, microbiome, de novo mutation, somatic DNA mutation, error rate, cellular reprogramming, tissue differentiation, 5′ methylation, cytosine, CpG dinucleotides, 5-methylcytosine, methyltransferases, DNMT3a, DNMT3b, DNMT1, Polycomb-group genes, methyl-CpG binding proteins, writers, erasers, readers, microRNA, H3K4me3, gene repression, Non-coding RNAs, Infrastructural ncRNA, ribosomal, transfer, small nuclear, small nucleolar RNA, regulatory ncRNA, microRNAs, long non-coding RNA, RNA-induced silencing complex, untranslated regions, RNA interference, post-transcriptional gene silencing, large intergenic non-coding RNAs, post-translational modifications, inter-nucleosomal interactions, small ubiquitin-like modifier, SUMOylation, glycosylation, hydroxylation, phosphorylation, sulfation, acetylation, citrullination, crotonylation, malonylation, ADP-ribosylation.

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Barrios N, Velázquez E, Velazquez F, Maidana M, Bordón J. Not Every Massive Cardiomegaly in a Newborn Infant is due to an Ebstein's Anomaly or a Large Pericardial Effusion. Newborn 2024; 3(3):233-237. DOI: 110.5005/jp-journals-11002-0100.

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Abstract: In neonates, massive cardiomegaly on chest X-rays is an infrequent but concerning finding. These observations are ascribed most frequently to tricuspid valve malformations as in Ebstein's anomaly and to large pericardial effusions. We recently treated a 40 weeks/3 kg male infant born to a 23-year-old primigravida mother after an uneventful, carefully followed pregnancy. The infant developed respiratory distress soon after birth, and a massively enlarged cardiac silhouette was noted on initial evaluation. We investigated the aforementioned possibilities of Ebstein's anomaly or a massive pericardial effusion, but this infant turned out to have a large intrathoracic cystic mass in the left hemithorax. The differential diagnosis was a bronchogenic vs gastrointestinal duplication cyst. The mediastinum was displaced towards the right side. The heart and major vessels were all normal in size. On postnatal day 8, a left posterolateral thoracotomy was performed, and a giant cystic tumor was dissected. There was a tense capsule attached to the lower lobe of the left lung, posterior pleura, esophagus, descending aortic artery, and diaphragm. The surrounding lung tissue was largely intact. Histopathology of the cyst wall showed features of both gastric and small intestinal mucosa, which was consistent with the findings seen in a broad group of anomalies known as bronchopulmonary foregut malformations. We need to consider a wider list of entities in the differential diagnosis of a massively enlarged cardiac silhouette in an infant with respiratory distress.

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Key scientific associations: neonate, respiratory distress, bronchogenic cyst, gastrointestinal duplication cyst, intra-thoracic cyst, bronchogenic cyst, gastrointestinal duplication cyst, fetal cardiomyopathy, cerebral/hepatic arterio-venous malformations, type 1 cystic adenomatoid malformation, parietal enhancement, posterolateral thoracotomy, muscularis propria, mother-infant dyad, bronchopulmonary foregut malformations, bronchogenic cyst, neuro-enteric cyst, enteric cyst.

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Jha VV, Arora G, Arora V. Two Novel Mutations Associated with Familial Chylomicronemia in a Neonate. Newborn 2024; 3(3):238-244. DOI: 10.5005/jp-journals-11002-0105.

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Abstract: We recently treated a 12-day-old male infant who was presented with respiratory distress, hepatosplenomegaly, and lipemia retinalis. The laboratory notified us that his blood samples were unusually viscous and pinkish-white and turned opaque milky white in about 10 minutes. The acute phase reactants were consistent with inflammation but the cultures remained sterile. Sera showed chylomicronemia with high triglyceride and cholesterol levels. We changed feedings to a special formula containing medium-chain fatty acids. Genetic analysis showed a novel homozygous mutation in the lipoprotein lipase (LPL) gene. In addition, he had a heterozygous missense variation in the sterol regulatory element-binding transcription factor 2 (SREBF2) gene. His father was also found to have hypertriglyceridemia and is being evaluated. This case reminds us yet again that not every infant with respiratory distress has an infection as the underlying cause. Timely diagnosis and intervention can improve outcomes.

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Key scientific associations: neonate, newborn, infant, consanguineous marriage, respiratory distress, hepatosplenomegaly, lipoprotein lipase, lipemia retinalis, medium-chain fatty acids, autosomal recessive, mutations, hypertriglyceridemia, hypertriglyceridemia, cholesterol, lipemia retinalis, sterol regulatory element-binding transcription factor 2, SREBP, triglyceride, homozygous, missense mutation, heterozygous, missense mutation, heparan sulfate proteoglycans, glycosyl phosphatidylinositol, lipoprotein lipids, transcriptional, posttranscriptional, translational, post-translational, apo-B48, lipase maturation factor 1, LMF1, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1, GPIHBP1, microsomal triglyceride transfer protein, MTP, LPL, LMF1, apo-CII, apo-A5, eruptive xanthomas, catalytically-inactive, chylomicronemia, compound heterozygosity, uniparental disomy, genitor, imprinting disorder, isodisomy, reduction-to-homozygosity, lomitapide, SCAP, SREBP-cleavage activating protein.