sNucConv: A bulk RNA-seq deconvolution method trained on single-nucleus RNA-seq data to estimate cell-type composition of human adipose tissues.

Deconvolution algorithms mostly rely on single-cell RNA-sequencing (scRNA-seq) data applied onto bulk RNA-sequencing (bulk RNA-seq) to estimate tissues' cell-type composition, with performance accuracy validated on deposited databases. Adipose tissues' cellular composition is highly variable, and adipocytes can only be captured by single-nucleus RNA-sequencing (snRNA-seq). Here we report the development of sNucConv, a Scaden deep-learning-based deconvolution tool, trained using 5 hSAT and 7 hVAT snRNA-seq-based data corrected by (i) snRNA-seq/bulk RNA-seq highly correlated genes and (ii) individual cell-type regression models. Applying sNucConv on our bulk RNA-seq data resulted in cell-type proportion estimation of 15 and 13 cell types, with accuracy of R = 0.93 (range: 0.76-0.97) and R = 0.95 (range: 0.92-0.98) for hVAT and hSAT, respectively. This performance level was further validated on an independent set of samples (5 hSAT; 5 hVAT). The resulting model was depot specific, reflecting depot differences in gene expression patterns. Jointly, sNucConv provides proof-of-concept for producing validated deconvolution models for tissues un-amenable to scRNA-seq.

At the threshold of viability: to resuscitate or not to resuscitate - the perspectives of Israeli neonatologists.

OBJECTIVE: This study aims to examine the perspectives of neonatologists in Israel regarding resuscitation of preterm infants born at 22-24 weeks gestation and their consideration of parental preferences. The factors that influence physicians' decisions on the verge of viability were investigated, and the extent to which their decisions align with the national clinical guidelines were determined. STUDY DESIGN: Descriptive and correlative study using a 47-questions online questionnaire. RESULTS: 90 (71%) of 127 active neonatologists in Israel responded. 74%, 50% and 16% of the respondents believed that resuscitation and full treatment at birth are against the best interests of infants born at 22, 23 and 24 weeks gestation, respectively. Respondents' decisions regarding resuscitation of extremely preterm infants showed significant variation and were consistently in disagreement with either the national clinical guidelines or the perception of what is in the best interest of these newborns. Gender, experience, country of birth and the level of religiosity were all associated with respondents' preferences regarding treatment decisions. Personal values and concerns about legal issues were also believed to affect decision-making. CONCLUSION: Significant variation was observed among Israeli neonatologists regarding delivery room management of extremely premature infants born at 22-24 weeks gestation, usually with a notable emphasis on respecting parents' wishes. The current national guidelines do not fully encompass the wide range of approaches. The country's guidelines should reflect the existing range of opinions, possibly through a broad survey of caregivers before setting the guidelines and recommendations.

Plasmids in the human gut reveal neutral dispersal and recombination that is overpowered by inflammatory diseases.

Plasmids are pivotal in driving bacterial evolution through horizontal gene transfer. Here, we investigated 3467 human gut microbiome samples across continents and disease states, analyzing 11,086 plasmids. Our analyses reveal that plasmid dispersal is predominantly stochastic, indicating neutral processes as the primary driver of their wide distribution. We find that only 20-25% of plasmid DNA is being selected in various disease states, constraining its distribution across hosts. Selective pressures shape specific plasmid segments with distinct ecological functions, influenced by plasmid mobilization lifestyle, antibiotic usage, and inflammatory gut diseases. Notably, these elements are more commonly shared within groups of individuals with similar health conditions, such as Inflammatory Bowel Disease (IBD), regardless of geographic location across continents. These segments contain essential genes such as iron transport mechanisms- a distinctive gut signature of IBD that impacts the severity of inflammation. Our findings shed light on mechanisms driving plasmid dispersal and selection in the human gut, highlighting their role as carriers of vital gene pools impacting bacterial hosts and ecosystem dynamics.

Cryptic diversity of cellulose-degrading gut bacteria in industrialized humans.

Humans, like all mammals, depend on the gut microbiome for digestion of cellulose, the main component of plant fiber. However, evidence for cellulose fermentation in the human gut is scarce. We have identified ruminococcal species in the gut microbiota of human populations that assemble functional multienzymatic cellulosome structures capable of degrading plant cell wall polysaccharides. One of these species, which is strongly associated with humans, likely originated in the ruminant gut and was subsequently transferred to the human gut, potentially during domestication where it underwent diversification and diet-related adaptation through the acquisition of genes from other gut microbes. Collectively, these species are abundant and widespread among ancient humans, hunter-gatherers, and rural populations but are rare in populations from industrialized societies thus indicating potential disappearance in response to the westernized lifestyle.

A transcriptomic examination of encased rotifer embryos reveals the developmental trajectory leading to long-term dormancy; are they "animal seeds"?

BACKGROUND: Organisms from many distinct evolutionary lineages acquired the capacity to enter a dormant state in response to environmental conditions incompatible with maintaining normal life activities. Most studied organisms exhibit seasonal or annual episodes of dormancy, but numerous less studied organisms enter long-term dormancy, lasting decades or even centuries. Intriguingly, many planktonic animals produce encased embryos known as resting eggs or cysts that, like plant seeds, may remain dormant for decades. Herein, we studied a rotifer Brachionus plicatilis as a model planktonic species that forms encased dormant embryos via sexual reproduction and non-dormant embryos via asexual reproduction and raised the following questions: Which genes are expressed at which time points during embryogenesis? How do temporal transcript abundance profiles differ between the two types of embryos? When does the cell cycle arrest? How do dormant embryos manage energy? RESULTS: As the molecular developmental kinetics of encased embryos remain unknown, we employed single embryo RNA sequencing (CEL-seq) of samples collected during dormant and non-dormant embryogenesis. We identified comprehensive and temporal transcript abundance patterns of genes and their associated enriched functional pathways. Striking differences were uncovered between dormant and non-dormant embryos. In early development, the cell cycle-associated pathways were enriched in both embryo types but terminated with fewer nuclei in dormant embryos. As development progressed, the gene transcript abundance profiles became increasingly divergent between dormant and non-dormant embryos. Organogenesis was suspended in dormant embryos, concomitant with low transcript abundance of homeobox genes, and was replaced with an ATP-poor preparatory phase characterized by very high transcript abundance of genes encoding for hallmark dormancy proteins (e.g., LEA proteins, sHSP, and anti-ROS proteins, also found in plant seeds) and proteins involved in dormancy exit. Surprisingly, this period appeared analogous to the late maturation phase of plant seeds. CONCLUSIONS: The study highlights novel divergent temporal transcript abundance patterns between dormant and non-dormant embryos. Remarkably, several convergent functional solutions appear during the development of resting eggs and plant seeds, suggesting a similar preparatory phase for long-term dormancy. This study accentuated the broad novel molecular features of long-term dormancy in encased animal embryos that behave like "animal seeds".

Comparison of three bioinformatics tools in the detection of ASD candidate variants from whole exome sequencing data.

Autism spectrum disorder (ASD) is a heterogenous multifactorial neurodevelopmental condition with a significant genetic susceptibility component. Thus, identifying genetic variations associated with ASD is a complex task. Whole-exome sequencing (WES) is an effective approach for detecting extremely rare protein-coding single-nucleotide variants (SNVs) and short insertions/deletions (INDELs). However, interpreting these variants' functional and clinical consequences requires integrating multifaceted genomic information. We compared the concordance and effectiveness of three bioinformatics tools in detecting ASD candidate variants (SNVs and short INDELs) from WES data of 220 ASD family trios registered in the National Autism Database of Israel. We studied only rare (< 1% population frequency) proband-specific variants. According to the American College of Medical Genetics (ACMG) guidelines, the pathogenicity of variants was evaluated by the InterVar and TAPES tools. In addition, likely gene-disrupting (LGD) variants were detected based on an in-house bioinformatics tool, Psi-Variant, that integrates results from seven in-silico prediction tools. Overall, 372 variants in 311 genes distributed in 168 probands were detected by these tools. The overlap between the tools was 64.1, 22.9, and 23.1% for InterVar-TAPES, InterVar-Psi-Variant, and TAPES-Psi-Variant, respectively. The intersection between InterVar and Psi-Variant (I âˆ© P) was the most effective approach in detecting variants in known ASD genes (PPV = 0.274; OR = 7.09, 95% CI = 3.92-12.22), while the union of InterVar and Psi Variant (I U P) achieved the highest diagnostic yield (20.5%).Our results suggest that integrating different variant interpretation approaches in detecting ASD candidate variants from WES data is superior to each approach alone. The inclusion of additional criteria could further improve the detection of ASD candidate variants.

Transcutaneous CO2 Monitoring in Extremely Low Birth Weight Premature Infants.

Extremely low birth weight (ELBW) premature infants are particularly susceptible to hypocarbia and hypercarbia, which are associated with brain and lung morbidities. Transcutaneous CO2 (TcCO2) monitoring allows for continuous non-invasive CO2 monitoring during invasive and non-invasive ventilation and is becoming more popular in the NICU. We aimed to evaluate the correlation and agreement between CO2 levels measured by a TcCO2 monitor and blood gas CO2 (bgCO2) among ELBW infants. This was a prospective observational multicenter study. All infants < 1000 g admitted to the participating NICUs during the study period were monitored by a TcCO2 monitor, if available. For each bgCO2 measured, a simultaneous TcCO2 measurement was documented. In total, 1828 pairs of TcCO2-bgCO2 values of 94 infants were collected, with a median (IQR) gestational age of 26.4 (26.0, 28.3) weeks and birth weight of 800 (702, 900) g. A moderate correlation (Pearson: r = 0.64) and good agreement (bias (95% limits of agreement)):(2.9 [-11.8, 17.6] mmHg) were found between the TcCO2 and bgCO2 values in the 25-70 mmHg TcCO2 range. The correlation between the TcCO2 and bgCO2 trends was moderate. CO2 measurements by TcCO2 are in good agreement (bias < 5 mmHg) with bgCO2 among premature infants < 1000 g during the first week of life, regardless of day of life, ventilation mode (invasive/non-invasive), and sampling method (arterial/capillary/venous). However, wide limits of agreement and moderate correlation dictate the use of TcCO2 as a complementary tool to blood gas sampling, to assess CO2 levels and trends in individual patients.

The Molecular Mechanisms Employed by the Parasite Myxobolus bejeranoi (Cnidaria: Myxozoa) from Invasion through Sporulation for Successful Proliferation in Its Fish Host.

Myxozoa is a unique group of obligate endoparasites in the phylum Cnidaria that can cause emerging diseases in wild and cultured fish populations. Recently, we identified a new myxozoan species, Myxobolus bejeranoi, which infects the gills of cultured tilapia while suppressing host immunity. To uncover the molecular mechanisms underlying this successful parasitic strategy, we conducted transcriptomics analysis of M. bejeranoi throughout the infection. Our results show that histones, which are essential for accelerated cell division, are highly expressed even one day after invasion. As the infection progressed, conserved parasitic genes that are known to modulate the host immune reaction in different parasitic taxa were upregulated. These genes included energy-related glycolytic enzymes, as well as calreticulin, proteases, and miRNA biogenesis proteins. Interestingly, myxozoan calreticulin formed a distinct phylogenetic clade apart from other cnidarians, suggesting a possible function in parasite pathogenesis. Sporogenesis was in its final stages 20 days post-exposure, as spore-specific markers were highly expressed. Lastly, we provide the first catalog of transcription factors in a Myxozoa species, which is minimized compared to free-living cnidarians and is dominated by homeodomain types. Overall, these molecular insights into myxozoan infection support the concept that parasitic strategies are a result of convergent evolution.

Oxygenation Instability during Bolus versus Continuous Feeding among Very Low Birth Weight Premature Infants, Supported by Noninvasive Ventilation: A Randomized Prospective Study.

OBJECTIVE: This study aimed to compare oxygenation instability, as documented by the oxygen saturation (SpO2) histograms, during bolus (over 30 minutes) versus continuous (over 2 hours) feeding among very low birth weight (VLBW) premature infants, supported with noninvasive ventilation (NIV). STUDY DESIGN: This was a randomized prospective study. VLBW infants supported with NIV received three consecutive feeds in a random order of bolus-continuous-bolus or continuous-bolus-continuous. During each feed, 30 minutes and 2 hours histograms were documented. RESULTS: Twenty-four infants (birth weight [mean ± standard deviation, SD] 820 ± 168 g, gestational age [mean ± SD] 27.0 ± 1.6 weeks) were included in our study (12 infants started with bolus feeding and 12 with continuous feeding) and 72 histograms were obtained (36 during bolus feeding and 36 during continuous feeding). No differences in mean fraction of inspired oxygen (FiO2), and number of apnea events were observed between the two feeding modes. Oxygenation instability as assessed by time spent in different SpO2 ranges and histogram types (stable or unstable) was comparable during bolus and continuous feedings. Changing feeding mode from bolus to continuous or vice versa did not significantly change the oxygenation instability of the group, though individual infants did show a consistence response to feeding length changes. CONCLUSION: Among VLBW infants supported with NIV, oxygenation instability, as documented by SpO2 histograms, was comparable between bolus and continuous feedings. Individual infants may benefit from specific feeding length, and this can be easily demonstrated by the SpO2 histograms. KEY POINTS: · Feeding length did not affect oxygenation instability of preterm infants on noninvasive respiratory Support.. · Oxygen saturation histograms allow objective quantification of oxygenation instability at the bedside.. · Individual infants benefit from specific feeding length, as demonstrated by SpO2 histograms..

Is there room for prompt routine ophthalmic examination in neonates with congenital cytomegalovirus (CMV) infection during the neonatal period?

PURPOSE: To establish the clinical necessity of routine targeted ophthalmic examination of newborns with congenital cytomegalovirus (CMV) infection during the neonatal period. METHODS: This retrospective study included consecutive neonates that were referred for ophthalmological screening within the context of a proven congenital CMV infection. The presence of CMV-related ocular and systemic findings was determined. RESULTS: Among the 91 patients included in this study, 72 (79.12%) were symptomatic with one or more of the following manifestations: abnormal brain ultrasound (42; 46.15%), small for gestational age (29; 31.87%), microcephaly (23; 25.27%), thrombocytopenia (14; 15.38%), sensory neural hearing loss (13; 14.29%), neutropenia (12; 13.19%), anemia (4; 4.4%), skin lesions (4; 4.4%), hepatomegaly (3; 3.3%), splenomegaly (3; 3.3%), direct hyperbilirubinemia (2; 2.2%). Not one single neonate in this cohort had any of the ocular findings surveyed. CONCLUSION: The presence of ophthalmological findings among neonates with congenital CMV infection during the neonatal period is infrequent, suggesting that routine ophthalmological screening may be safely deferred for the post-neonatal period.

The effect of changing respiratory rate settings on CO2 levels during nasal intermittent positive pressure ventilation (NIPPV) in premature infants.

OBJECTIVE: To examine the change in CO2, when applying NIPPV with either a low or a high rate in stable premature infants. STUDY DESIGN: Prospective, controlled, crossover study. Preterm infants on NIPPV were monitored by tcCO2 during two rate changes switching every hour between high (30 bpm) and low (10 bpm) set rates. RESULTS: Fifty premature infants (mean ± SD: 28.3 ± 2.4 weeks' gestation) were enrolled. Each infant had two rate changes; therefore, a hundred rate changes were studied. The mean change in tcCO2, i.e., ΔtcCO2 (95% confidence-interval), was -1.1 (-2.3 to 0.1) mmHg for increasing rate from low to high, and 0.46 (-0.49 to 1.41) mmHg for decreasing rate from high to low. CONCLUSION: Multiplying or dividing the rate settings by three did not significantly change the tcCO2 readings an hour after the change. These findings could affect the management of ventilation settings of NIPPV in premature infants. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov ID: NCT04836689 , The name of the trial registry: "Influence of Respiratory Rate Settings on CO2 Levels During Nasal Intermittent Positive Pressure Ventilation (NIPPV)."

Oxygen saturation histogram classification system to evaluate response to doxapram treatment in preterm infants.

BACKGROUND: An oxygen saturation (SpO2) histogram classification system has been shown to enable quantification of SpO2 instability into five types, based on histogram distribution and time spent at SpO2 ≤ 80%. We aimed to investigate this classification system as a tool to describe response to doxapram treatment in infants with severe apnea of prematurity. METHODS: This retrospective study included 61 very-low-birth-weight infants who received doxapram. SpO2 histograms were generated over the 24-h before and after doxapram start. Therapy response was defined as a decrease of ≥1 histogram types after therapy start. RESULTS: The median (IQR) histogram type decreased from 4 (3-4) before to 3 (2-3) after therapy start (p < 0.001). The median (IQR) FiO2 remained constant before (27% [24-35%]) and after (26% [22-35%]) therapy. Thirty-six infants (59%) responded to therapy within 24 h. In 34/36 (94%) of the responders, invasive mechanical ventilation (IMV) was not required during the first 72 h of therapy, compared to 15/25 (60%) of non-responders (p = 0.002). Positive and negative predictive values of the 24-h response for no IMV requirement within 72 h were 0.46 and 0.94, respectively. CONCLUSIONS: Classification of SpO2 histograms provides an objective bedside measure to assess response to doxapram therapy and can serve as a tool to detect changes in oxygenation status around respiratory interventions. IMPACT: The SpO2 histogram classification system provides a tool for quantifying response to doxapram therapy. The classification system allowed estimation of the probability of invasive mechanical ventilation requirement, already within a few hours of treatment. The SpO2 histogram classification system allows an objective bedside assessment of the oxygenation status of the preterm infant, making it possible to assess the changes in oxygenation status in response to respiratory interventions.

Oxygenation in the NICU: there is more to it than meets the eye.

IMPACT: Dormishian and colleagues in their study address an issue that care teams in the NICU encounter on a daily basis, regarding motion artifacts during oxygenation monitoring. In our commentary, we discuss the available tools that allow continuous noninvasive monitoring of oxygenation in the NICU, and modalities that increase the time premature infants spend in the desired SpO2 range and impact their clinical outcomes.

Prenatal exposure to heavy metal mixtures and anthropometric birth outcomes: a cross-sectional study.

BACKGROUND: Numerous studies have suggested significant associations between prenatal exposure to heavy metals and newborn anthropometric measures. However, little is known about the effect of various heavy metal mixtures at relatively low concentrations. Hence, this study aimed to investigate associations between prenatal exposures to a wide range of individual heavy metals and heavy metal mixtures with anthropometric measures of newborns. METHODS: We recruited 975 mother-term infant pairs from two major hospitals in Israel. Associations between eight heavy metals (arsenic, cadmium, chromium, mercury, nickel, lead, selenium, and thallium) detected in maternal urine samples on the day of delivery with weight, length, and head circumference at birth were estimated using linear and Bayesian kernel machine regression (BKMR) models. RESULTS: Most heavy metals examined in our study were observed in lower concentrations than in other studies, except for selenium. In the linear as well as the BKMR models, birth weight and length were negatively associated with levels of chromium. Birth weight was found to be negatively associated with thallium and positively associated with nickel. CONCLUSION: By using a large sample size and advanced statistical models, we could examine the association between prenatal exposure to metals in relatively low concentrations and anthropometric measures of newborns. Chromium was suggested to be the most influential metal in the mixture, and its associations with birth weight and length were found negative. Head circumference was neither associated with any of the metals, yet the levels of metals detected in our sample were relatively low. The suggested associations should be further investigated and could shed light on complex biochemical processes involved in intrauterine fetal development.

Cardiopulmonary Exercise Testing in Childhood in Late Preterms: Comparison to Early Preterms and Term-Born Controls.

Background: Late preterm (340−366 weeks gestational age [GA]) infants may have abnormal pulmonary development and possible exercise physiology parameters. We aim to assess the effect of late prematurity on exercise capacity in childhood and to compare it to early preterm (EP) (born < 300 GA), and to term healthy control (TC) (>370 week GA). Methods: Late preterm and early preterm (7−10 years) completed a cardiopulmonary exercise test (CPET) and spirometry and were compared to EP and to TC. Results: Eighty-four children (age 9.6 ± 1.0 years, 48% girls) participated. Twenty-one former LP were compared to 38 EP (15 with Bronchopulmonary dysplasia (BPD) [EP+], 23 without BPD [EP−]) and to 25 TC children. Peak oxygen uptake (peakV̇O2) was statistically lower than in the TC, but within the normal range, and without difference from the EP (LP 90.2 ± 15.1%, TC 112.4 ± 16.9%, p < 0.001; EP+ 97.3 ± 25.5%, EP− 85.4 ± 20.8%, p = 0.016 and p < 0.001, respectively, when compared with TC). Lung function (FEV1) was lower than normal only in the EP+ (75.6 ± 14.9% predicted, compared with 12.5 ± 87.8 in EP−, 87.5 ± 16.9 in LP and 91.0 ± 11.7 in TC). Respiratory and cardiac limitations were similar between all four study groups. Conclusions: This study demonstrated lower exercise capacity (peakV̇O2) in former LP children compared with healthy term children. Exercise capacity in LP was comparable to that of EP, with and without BPD. However, the exercise test parameters, specifically peakV̇O2, were within the normal range, and no significant physiological exercise limitations were found.

Continuous versus Bolus Gastric Tube Feeding in Very Low Birth Weight Infants Supported with Noninvasive Respiratory Support: A Randomized, Pilot Study.

OBJECTIVES: This study aimed to compare time to full feeding (TFF) between continuous gastric feeding (CGF) and bolus feeding (BF) in very low birth weight (VLBW) infants supported with noninvasive ventilation (NIV) and to evaluate feasibility and identify methodological pitfalls for future large-scale studies. STUDY DESIGN: This study is a randomized controlled, prospective, pilot study. VLBW premature infants, supported with NIV, were randomized while still on trophic feeding <20 mL/kg/day to receive feeding over 2 hours of CGF or over 15- to 30-minute BF. The primary outcome was TFF. Analysis was done by intention to treat. RESULTS: Overall, 32 infants were included in this analysis, 17 in the CGF group and 15 in the BF group. Infants in the CGF group were significantly younger than the BF group (mean ± standard deviation [SD] gestational age [GA] 26.9 ± 1.2 vs. 28.9 ± 1.5 weeks, respectively). TFF was comparable with median (interquartile range [IQR]) for the two groups, 10.0 (10.0, 19.0) days in the BF group versus 12.0 (9.0, 13.0) days in the CGF group (p = 0.59). Feeding length was not found to significantly affect TFF in multivariate analysis correcting for GA. Groups were comparable in weight gain, gastrointestinal complications, length of NIV, bronchopulmonary dysplasia incidence, and age at discharge. Most infants from both groups (60% of BF and 70% of CGF) required changes in feeding length. CONCLUSION: In this pilot study, among VLBW infants supported with NIV, TFF was comparable between the BF and CGF groups. These results should be interpreted with caution due to the small sample size and despite the multivariate analysis correcting for the different GA. Interestingly, most infants required changes in feeding length regardless of their allocation. This feasibility study emphasizes the need for careful attention to randomization and strict feeding protocols including criteria for switching allocation in future large-scale studies aimed at determining the preferred feeding length during NIV in VLBW infants. KEY POINTS: · Among infants supported with NIV, length of feeding affects gastric venting.. · BF might increase gastrointestinal reflux, while continuous feeding hinders gastric decompression.. · Among infants supported by NIV, feeding tolerance was comparable between bolus and continuous groups..

Ventilation-induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with prophylactic anti-inflammatory therapeutics.

Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite the maintenance of blood oxygen homeostasis during ventilatory support. The biotrauma hypothesis advocates that mechanical forces from invasive ventilation trigger immunological mediators that spread systemically. Yet, how these forces elicit an immune response remains unclear. Here, a biomimetic in vitro three-dimensional (3D) upper airways model allows to recapitulate lung injury and immune responses induced during invasive mechanical ventilation in neonates. Under such ventilatory support, flow-induced stresses injure the bronchial epithelium of the intubated airways model and directly modulate epithelial cell inflammatory cytokine secretion associated with pulmonary injury. Fluorescence microscopy and biochemical analyses reveal site-specific susceptibility to epithelial erosion in airways from jet-flow impaction and are linked to increases in cell apoptosis and modulated secretions of cytokines IL-6, -8, and -10. In an effort to mitigate the onset of biotrauma, prophylactic pharmacological treatment with Montelukast, a leukotriene receptor antagonist, reduces apoptosis and pro-inflammatory signaling during invasive ventilation of the in vitro model. This 3D airway platform points to a previously overlooked origin of lung injury and showcases translational opportunities in preclinical pulmonary research toward protective therapies and improved protocols for patient care.

An Approach to Nasopharyngeal Mass in Newborns: Case Series and Systematic Literature Review.

OBJECTIVE: Congenital nasopharyngeal masses (CNMs) are rare. Presenting symptoms vary, and the differential diagnoses cover a wide spectrum of possibilities. As it is uncommon, most examples discussed in literature are described as case reports or series. Guidelines on CNM patient management do not exist. In this study, we present two (2) cases of neonates with CNMs that were encountered at our tertiary center. Additionally, to best elaborate a comprehensive, case-based approach to CNM management, we offer an up-to-date, diagnosis-to-treatment review of current literature. METHODS: Case series and systematic literature review. RESULTS: Twenty-eight (28) studies are included since January 2000 to October 2021, with a total of 41 cases. Most common diagnosis was teratoma (78%). Female-to-male ratio was 2.5:1. Twenty percent of cases presented prenatally with polyhydramnios or elevated alpha-fetoprotein. Postnatally, the presenting symptoms most frequently encountered were respiratory distress (78%), oral mass (52%), and feeding difficulties (29%). Seventy-five percent of affected newborns showed symptoms within the first 24 hours of life. Forty percent of cases had comorbidities, especially in the head and neck region. CONCLUSIONS: Congenital nasopharyngeal masses can be detected antenatally, or symptomatically immediately after birth. Airway protection is a cornerstone in the management. Selecting the right imaging modality and convening a multidisciplinary team meeting are important toward the planning of next steps/therapeutic approach. Typically, a transnasal or transoral surgical approach will be deemed sufficient to address the problem, with a good overall prognosis.