He L, Harold SF, Frydrysiak–Brzozowska A. Big Ideas Start Small. Newborn 2025; 4(4):iv-xiv. DOI: 10.5005/newborn-4-4-iv.

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Alghnimei N, Yaquob Daghriri Y, Alhwiti A, et al. Screening for Developmental Dysplasia of the Hip in Saudi Arabia: Technically Feasible, but Social Barriers Persist. Newborn 2025; 4(4):159–164. DOI: 10.5005/jp-journals-11002-0140.

 

Abstract:

Objectives: Developmental dysplasia of hip (DDH) is a complex spectrum of hip abnormalities, where timely diagnosis and management can improve outcomes. Evaluation soon after birth and during early infancy can help identify at-risk infants. In this study, we present a brief review of our DDH screening program and a retrospective observational study of the barriers to DDH screening/follow-up in a large clinical cohort of infants in the Kingdom of Saudi Arabia (KSA).
Methods: This retrospective observational cohort study was conducted in the KSA for an 8-month period between December 2023 and July 2024. We evaluated infants with one risk factor and/or positive clinical exam for DDH and followed them with at least one in-person visit, followed by direct clinical and/or telephone contact. A standardized questionnaire was used to understand parental perception and factors affecting compliance with the screening process.
Results: We followed a cohort of 3,598 infants; 95 were identified as high-risk for DDH. The most frequent prenatal risk factors were breech deliveries, positive family history, preterm birth, and twin gestation. In the DDH follow-up program, the overall compliance rate was 47/95 (49.5%). The major reason for missing the other 48 (50.5%) at-risk patients was ineffective communication. The contact information had not been recorded correctly in 36 of 48 cases (75%). In 11 (23%), parents were not aware of the importance of timely diagnosis and close follow-up. In 13 (27%), the primary difficulty was access to medical support because of long distance/difficult terrain. Some families either did not believe in the need for screening [2/48 (4.2%)] or missed their appointment [4/48 (8.3%)]. In some cases, medical responsibilities related to other members in the household and cultural beliefs about DDH screening may have contributed to noncompliance. Improvement in parental education regarding DDH raised the compliance rate with follow-up by 20%.
Conclusion: Parental noncompliance with DDH follow-up screening programs is influenced by multiple factors. The most frequent reasons were related to difficulties with communication and inaccuracy of parental contact information. Parental education about the importance of timely diagnosis of DDH and the risks of delayed intervention is essential. The geographic location of the families from medical facilities was also important; the access through long distances and/or difficult terrain needs to be improved.

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​Key scientific associations: Barriers, Education, Healthcare access, Hip displacement, Hip dislocation, Neonates, Parental compliance, Screening programs, Telemedicine, standardized questionnaires, consanguinity, swaddling, torticollis, plagiocephaly, metatarsus adductus, calcaneovalgus deformity, Ortolani, Barlow, NIPE handbook, Graf technique, Harcke dynamic, Hilgenreiner's line, acetabular index, lateral triradiate cartilage, Perkin’s line, Shenton’s line, superior pubic ramus, ossification nucleus.

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Das JK, Maheshwari A. A High-throughput Analysis of Gene Expression in the Intestine in Severe Neonatal Anemia. Newborn 2025; 4(4):165–177. DOI: 10.5005/jp-journals-11002-0145.

 

​Abstract:

Background: In recent years, most centers caring for premature and critically ill infants have adopted restrictive red blood cell (RBC) transfusion guidelines to minimize transfusions in asymptomatic infants unless the hematocrit drops below 20–22%. However, there is renewed awareness about the risks of anemia in neonates. We have shown that severely anemic human infants show higher intestinal permeability, bacterial translocation, and both local/systemic inflammation. In this study, we used an established mouse pup model to investigate the effect of severe anemia in the intestine using an open-ended, high-throughput approach using microarrays.
Materials and methods: C57BL/6 mouse pups were rendered severely anemic (hematocrits = 20–24%, n = 14 in control and anemic arms) by serial phlebotomies on postnatal days 2–10. The ileocecal region was processed to extract mRNA, and gene expression was measured using open-ended, high-throughput microarray analyses, using a threshold for altered gene expression of ±1.5-fold. To ensure the effectiveness of the analyses and avoid unknown errors, the authors compiled their own robust bioinformatics pipelines for microarray data processing, principal component analysis (PCA), screening of differentially expressed genes (DEGs), hierarchical clustering analysis, gene-set enrichment analysis, and quantitative analysis.
Results: We first conducted PCA using log-transformed gene expression data. The visualization of a few principal components (PCs) in intestinal tissue samples after batch-effect correction showed a distinct separation between control and anemia groups. Comparison of the anemic vs control samples showed 2,826 DEGs, with 1,041 upregulated and 1,825 downregulated genes. Enrichment analyses were conducted, targeting gene ontology (GO) for biological processes (BPs), molecular functions (MFs), and cellular components (CC). Two major pathway analyses were also used. The study showed that severe neonatal anemia has a significant biological impact in the gastrointestinal tract, particularly on the maintenance of epithelial cell integrity and gut leakiness, local innate immune responses, and inflammation.
Conclusions/significance: We reviewed the upregulated and downregulated DEGs in this neonatal mouse model of severe anemia. However, even though many of these genes exert similar-looking pathophysiological effects, the reasons for some being induced and others being suppressed were not readily evident. Similarly, the patterns seen in altered expression of some genetic pathways identified in ontology analyses could not be explained. The stage of development, and in humans, transfused blood (composition of the hemoglobin with adult and fetal isoforms) can be important confounding factors and need study. Overall, severe anemia induces significant pathophysiological changes in gut barrier function, innate immune responses, and inflammation.

 

​​Key scientific associations: Adenylate kinase 4, Atos homolog A, Bioinformatics, Carbamoyl phosphate synthetase 1, Caspase-1, Critical developmental epochs, CSA-conditional, Cyclin G2, Cytochrome P450 family 27 subfamily A polypeptide 1, Dyskeratosis congenita 1, Erythropoietin, Fatty acid binding protein 4, Fetal hemoglobin, FITC-dextran, FK506 binding protein 5, Gene expression noise, Gene ontology, Gene Set Enrichment Analysis, Hierarchical clustering of differentially expressed genes, Highly transfused population, High-throughput approach, Homeobox C6, Hyaluronan and proteoglycan link protein 1, Infant, Inflammation, Integrin α2, Intestinal development, Intestine, Ki-67, Kinesin 11, Kinesin 4, k-mer, Kyoto Encyclopedia of Genes and Genomes, Linear models for microarray data, Log2 transformation, Log-fold change, Matrix Gla protein, MEF2B, Metadata, Mitogen-activated protein kinase 1 interacting protein 1, Multi-array Average, Myelin basic protein, Myocyte enhancer factor 2B (MEF2B), NADPH oxidase 4, NADPH oxidase activator 1, Necrotizing enterocolitis, Neonatal anemia, Neuregulin 1, Newborn, Nucleotide sequence, Oxygen affinity, Phlebotomy, Physiological nadir, Pipelines, Principal component analysis, Proliferation-associated 2G4, Prolyl endopeptidase, Protein arginine N-methyltransferase 5, Reactome, Red blood cell life span, Red blood Let it be, Robust multi-array average, RStudio, Software applications, Soluble (GPT/ALT, cytosolic alanine aminotransferase), Solute carrier family 17 member 8, Solute carrier family 23 member 4, Splanchnic perfusion, T cell activation-dependent protein, Thyrotroph embryonic factor, Vascular endothelial growth factor A, Volcano plot, Zinc finger and BTB domain containing 16.

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Kaushal M, Balla KC. Clinical Procedures: Use of Peripherally Inserted Central Catheters in Neonates. Newborn 2025;4(4):178–180. DOI: 10.5005/jp-journals-11002-0143. 

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Abstract: Peripherally inserted central catheters (PICCs) are widely used in neonatal intensive care units (NICUs) to provide durable central venous access in premature/critically ill infants. Point-of-care ultrasound (POCUS)-guided PICC insertion has improved the first-pass success rates of insertion of PICC lines, reducing complications and minimizing radiation exposure from repeated X-rays. This article outlines an evidence-based, standardized approach to PICC insertion, care, and verification in neonates.

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​​Key scientific associations: Basilic, Brachial, Cavoatrial junction, Cephalic, Coagulopathy, Cyanoacrylate glue, Great saphenous vein, High-frequency linear probe, Infant, Median cubital vein, Micro‑Seldinger technique, Newborn, Peripherally inserted central catheter, Point-of-care ultrasound, Polyurethane, Radiation exposure, Silicone, Vesicant medications.

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Singh S, Kaushal M, Guaragni B, et al. Systematized Systemic Sonographic Surveillance (S4). Newborn 2025;4(4):181–193. DOI: 10.5005/jp-journals-11002-0142. 

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Abstract: We are developing a systematized systemic sonographic surveillance (S4) program as a structured, sonographic technology-enabled extension of the physical examination of newborn infants. The philosophy of S4 differs from point-of-care ultrasound (POCUS), which is known for post hoc bedside confirmation/assessment/temporal monitoring of organ-system injury in at-risk/critically-ill patients. Systematized systemic sonographic surveillance utilizes radiation-free, real-time imaging for a priori assessment of risk or detection of sub-clinical lesions. We examine the brain (growth, hemorrhages), heart (preload, contractility), lungs (edema, atelectasis, consolidation, effusions, and pneumothorax), liver (size, parenchymal abnormalities, vascular complications), bowel (edema, contractility, ascites, early detection of sub-clinical necrotizing enterocolitis), urogenital tract, spine, and hips (developmental dysplasia). Visual guidance can also help in the placement of central lines and successful atraumatic performance of lumbar punctures (LPs). Systematized systemic sonographic surveillance can also reduce the duration of training and the need for sedation and transport for the evaluation of patients. Increased efficiency in clinical procedures may reduce the duration and intensity of pain and, consequently, have a positive impact on development. To summarize, sonographic surveillance could improve clinical decision-making and neonatal intensive care unit (NICU) outcomes. The costs of infrastructural enhancements in sonography still need evaluation vis-à-vis potential savings from reduced needs for disposables, short- and long-term morbidity, and the length of hospital stay.

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​Key scientific associations: A-lines, B-lines, Collapsibility index, Developmental dysplasia of the hip, Distensibility index, Dynamic LP, Endotracheal tube tip position, Graf classification, Hemodynamics, Hepatization, Intraventricular hemorrhage, Lung ultrasound, Lung ultrasound score, Multi-organ sonography, Neonatal intensive care unit, Neonate, Percutaneous central catheters, Point-of-care ultrasound, Screening, Shred sign, Static LP, Systematized systemic sono-surveillance, Training barriers, Umbilical arterial line, Umbilical venous line, Vascular access guidance, α-angle, β-angle.

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Singh S, Buddington SS, Huseynova R. Ethical Challenges in Neonatal Life Support. Newborn 2025;4(4):194–202. DOI: 10.5005/jp-journals-11002-0144. 

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Abstract: Advancements in neonatal intensive care have dramatically improved survival of extremely preterm and critically ill newborns while simultaneously intensifying ethical dilemmas surrounding futility, parental authority, best interests of the child, and resource allocation. This narrative review examines the application of the four principles of biomedical ethics to contemporary neonatal decision-making, landmark legal cases [Baby Doe, Baby K, Groningen Protocol, Charlie Gard, and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) babies], and persistent controversies in periviability, complex congenital anomalies, neonatal euthanasia, and emerging biotechnologies. Special attention is given to prognostic uncertainty, disability-rights critiques, global disparities, the risks and promises of artificial intelligence (AI) in prognostication, and the ongoing prohibition of heritable genome editing. The article concludes that neonatal ethics remains deeply contested because it confronts fundamental societal values regarding suffering, disability, and the worth of nascent human life, and calls for enhanced international collaboration, evidence-based shared decision-making, and culturally sensitive consensus guidelines, with a potential leadership role for the Global Newborn Society (GNS).

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Key scientific associations: Artificial intelligence, Baby Doe, Baby K, Best interests, Charlie Gard, CRISPR, Disability rights, Extreme prematurity, Futility, Genome editing, Groningen protocol, Infant, Neonatal ethics, Neonatal euthanasia, Neonate, Newborn, Parental autonomy, Periviability, Prognostic uncertainty, Quality of life, Shared decision-making, Withholding/withdrawing treatment.

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Prasad CS, Maheshwari A. Maternal Determinants of Neurodiversity in the Developing Brain: An Integrative Review of Biological, Environmental, and Psychological Factors. Newborn 2025;4(4):203–220. DOI:10.5005/jp-journals-11002-0147.

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Abstract: Neurodevelopmental delay is a major concern for obstetricians, neonatologists, and pediatricians all over the world. However, more recently, a view is emerging that we need to be cognizant of neurodiversity, a natural variation in cognitive and behavioral traits observed across individuals. Many differences in the human brain originate in the earliest developmental periods, when maternal biological signals and environmental conditions shape the fetal neural architecture. These temporal windows prior to conception, during embryogenesis, and fetal development are marked by significant plasticity and possibly shape lifelong neurodevelopment. The structural and functional changes can be affected by maternal metabolic, endocrine, immune, and psychosocial states, which act through the placenta to influence neurogenesis, synaptogenesis, and the assembly of large-scale networks. Differences in thinking, learning, attention, and behavior are a normal part of human diversity. Hence, conditions such as autism, attention-deficit and hyperactivity disorder (ADHD), and dyslexia might not be true deficits but alternative ways of experiencing and interacting with the outside world. The acceptance of these special needs as neurodiversity, not neurological deficits, promotes acceptance, inclusion, and support, and encourages societies, schools, and workplaces to value diverse cognitive strengths while providing appropriate accommodations for individual needs.

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Key scientific associations: 11β-hydroxysteroid dehydrogenase type II, Arsenic, Attention-deficit and hyperactivity disorder, Autism, Cortical layering, Dendritic arborization, Developmental origins of neurodevelopment, DNA methylation, Dyslexia, Epigenetic clock, Epigenetic drift, Epigenetic programming, Fetal signaling, Gamete quality, Heavy metals, Histone modifications, Infant, Interleukin-17A, Intimate partner violence, Ionizing medical radiation, Lead, Legal liability, Leptin signaling, Low-frequency electromagnetic fields, Maternal biological signals, Methylmercury exposure, Microbial seeding, Microglial maturation, Microglial priming, Mitochondrial DNA, Network topology, Neural progenitor proliferation, Neurodevelopmental disorders, Neurodevelopmental trajectories, Neuronal migration, Nitrogen dioxide, Non-coding RNA, Non-ionizing radiofrequency, Omega-3-long-chain polyunsaturated fatty acids, Organophosphate pesticides, Periconceptional folate, Phthalates, Plastics, PM10, PM2.5, Polybrominated diphenyl ethers, Synaptic pruning, Synaptogenesis, Tryptophan–kynurenine pathway, White matter scaffolding.

 

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Khare AK, Tanger RC, Baindur AJ. Case Report: A Congenital Pouch Colon with Anorectal Malformation and Associated Anomalies. Newborn 2025;4(4):221–224. DOI: 10.5005/jp-journals-11002-0146.

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Abstract:

Background: Congenital pouch colons (CPCs) are rare congenital malformations that are seen in the Indian Subcontinent and the surrounding region. These patients show major dilatations in one/more segments of the entire colon that are often associated with an anorectal malformation (ARM) and/or a fistulous communication with the distal urogenital tract. Many also show vesicoureteral reflux, hydronephrosis, hypospadias, a bicornuate/septate uterus, an absent/double appendix, a Meckel’s diverticulum, rectal atresia, sacral agenesis, and congenital heart defects. This case shows that timely identification and management of CPCs can improve the outcome of these patients.
Case presentation: We recently treated a four-day-old full-term, small-for-gestation female infant weighing 2.3 kg, who was presented with vomiting, abdominal distension, and had been passing stools through a single cloacal opening. An erect radiogram showed a massive colonic gas shadow on the left side that displaced the whole small bowel towards the right. An inverted X-ray showed a high anorectal malformation. Cystoscopy showed a constricted neck of the bladder and a bicornuate uterus. Hysteroscopy, and then an exploratory laparotomy confirmed the presence of a uterocolonic fistula, a massivelydilated pouch colon, a double appendix, and a Meckel’s diverticulum. The fistula was ligated, and a pouch ostomy was done. A review of the case showed that she had a type-2 CPC with cloaca, a colon-uterine fistula, a bicornuate uterus, double appendix, and a Meckel’s diverticulum. The infant stabilized over the next few days and was discharged from the hospital. She is being followed up and is progressing well.
Conclusion: Congenital pouch colons are complex congenital anomalies that can benefit from early identification and proper management. The condition is seen more frequently in males and is promptly diagnosed during the neonatal period due to abdominal distention, absence of anus, and intestinal obstruction. It is managed surgically depending on its type, with timely diagnosis and management. Congenital pouch colon is a rare but important condition where timely diagnosis and management can improve outcomes.

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Key scientific associations: Neonate, Baby, Autosomal recessive polycystic kidney disease, Biliary hamartomas, Caroli disease, Caroli syndrome, Congenital hepatic fibrosis, Focal intrahepatic biliary dilation, Infant, Oligohydramnios, Polycystic kidney and hepatic disease 1, Renal tubular ectasia, von Meyenburg complexes.

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Guaragni B. Advances in Viscoelastic Coagulation Monitoring. Newborn 2025;4(4):225–227. DOI: 10.5005/jp-journals-11002-0139.

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Abstract: Bleeding due to maturational and acquired coagulation disorders is seen frequently in premature/critically ill neonates. Viscoelastic coagulation monitoring (VCM) has been an exciting advance in the evaluation of blood clot formation, stabilization, and dissolution. Unlike the conventional evaluation of prothrombin time/international normalized ratio and activated partial thromboplastin time that are performed on plasma and do not provide information about platelets and fibrin cross-linking, viscoelastic tests (VETs) analyze whole blood and provide a global overview of the adequacy of clotting factors, fibrinogen, platelet function, red blood cells, and fibrinolytic processes. In the past few years, several cartridge-based devices have become available that do not need controlled pipetting. One VCM utilizes a miniature sensor without any moving mechanical parts to measure clot stiffness. It analyzes the coagulation state in a whole blood sample with a low-amplitude rotational or oscillatory force in less than 1 hour; it is portable, easy to use, and the small blood volume can be obtained from a heel stick. In this brief communication, the authors report VCM findings from a 1-day-old premature infant with hypofibrinogenemia and from a 5-day-old control of comparable gestational age. The altered parameters suggested suboptimal clot strength. These newer cartridge-based methods are being continuously improved; some instruments maintain the core VET principles of thromboelastography (TEG) and rotational thromboelastometry (ROTEM) but are being advanced with microfluidic cartridges and resonance-based detection instead of the rotating cup/pin of legacy devices, reducing sample handling and operator workload. Another ultrasound-based method measures the stiffness/shear modulus of whole blood as it clots. To reiterate, VETs can potentially improve hemostatic management, reduce unnecessary transfusions, and enhance patient outcomes. Further evaluation is definitely needed, but these tests could make a difference in the management of premature/critically ill infants.
 

Key scientific associations: Amplitude, α-angle (rate of clot formation), Cartridge-based coagulation monitors, Clot formation time, Clot initiation, Clot kinetics, Clot strength, Clot strengthening, Clotting, Coagulation, Coagulation index, Clotting time, DIC, Estimated percentage of lysis, Fibrin activity, Fibrinolysis, Fibrin strands, Hypofibrinogenemia, Maximum clot strength, Maximum clot firmness, Premature, Shear modulus of whole blood, Thromboelastography, Thromboelastometry, Viscoelastic coagulation monitor.