Neonatal diffuse cutaneous mastocytosis (NDCM) is defined as the infiltration of the epidermis by a clonal proliferation of mast cells, observed at birth, without initial signs of systemic involvement. The typical driver mutation is located in the KIT gene. We report a rare case of a boy, born at term, presenting already at birth with generalized subcutaneous nodules, on the face, scalp, trunk, back, hands, and feet. The spleen, liver and inflammatory markers were normal at birth. Tryptase was significantly elevated. Bone marrow biopsy showed no mast cell involvement at age 2 months. A punch biopsy at age 2 months revealed CD117-positive cells diffusely infiltrating the skin, with subsequent DNA NGS sequencing for the formalin fixed paraffin embedded tissue (FFPE) identifying the pathogenic NM_000222.3:c.1504_1509dup; p.(Ala502_Tyr503dup) variant in the KIT gene previously associated with cutaneous mastocytosis. At 2 years follow-up, he had splenomegaly and multiple cervical, and inguinal adenopathy while the skin nodules persisted especially on the scalp with accompanying pruritus. He received oral and local sodium cromoglycate, oral antihistamines, antibiotic cream for skin infection, and iron supplementation, however compliance to treatment was relatively low. The prognosis is difficult to predict, as he developed systemic involvement, failure to thrive and mild psychomotor delay. A case aggregation of NDCM reported in the literature was performed to provide a comprehensive overview of this rare pathology, to better understand the prognosis. NDCM is a life-threatening disease with severe complications. Almost half had severe complications, such as mast hepatosplenomegaly, adenopathy, bacterial infections, mast cell leukaemia, and systemic involvement.

Background: Despite tremendous efforts to reduce neonatal mortality worldwide and in 24 Ethiopia, there is the country is one of the countries with highest neonatal morbidity and health 25 losses. Never the less, the past three decades’ national trend and subnational distribution of 26 neonatal morbidity and mortality and its health loss in Ethiopia, was not well documented. 27 Hence, this study had aimed to analyze the trend and distributions as well as health losses 28 resulting from neonatal morbidity in the past three decades in Ethiopia, 2019. 29 Objective: To assess the national trend and sub national distributions of neonatal morbidity and 30 neonatal mortality in the previous three decades by using Global Burden of Diseases, 2019 data. 31 Methods: The data sources were primary and secondary data related to risk factors, morbidity, 32 disability, deaths, Disability Adjusted Life Years, Years Lived with Disability and Years Life Lost 33 were collected form case studies and case series, household surveys, socio-demographic surveys 34 and surveillances, health facilities surveys, Health facility observations and interviews and 35 published and unpublished literatures. The prevalence, deaths and health losses were calculated 36 by using embedded model. The study period covered from 1990 to 2019. Results were presented 37 buy using texts, tables and graphs. 38 Results: Seventy percent of neonatal disorders had occurred among early neonates aged 0 to 6 39 days. Between 1990 and 2019, the national prevalence of neonatal disorders had increased by 40 47% in to 28,319 (95% UI, 25646-30,361). Bet Similarly, the highest number of neonatal deaths 41 caused by neonatal sepsis had shifted from Southern Nations Nationalities and Peoples region to 42 Oromia region while Harari remains to bear the lowest burden in the last three decades. The 43 highest and the lowest YLL as a result of neonatal disorders had occurred in Oromia 44 [(2,753,038,95% UI, 2,184,142-3,497-926) and Amhara 1,360,847 [(95% UI, 95% UI, 45 1,062,660-1,762,028)] regions respectively. Unlike other regions, Addis Ababa had the highest 46 (52%) prevalence of preterm birth in 2019 47 Conclusion and Recommendation: About seven in ten of neonatal death had occurred among 48 early neonates indicating narrowed occurrence of the event. The highest and the lowest number 49 of neonatal death and health loss had occurred in Oromia and Harari regions respectively. The 50 main causes of death were neonatal sepsis and other infections, neonatal preterm, hemolytic 51 disease and other jaundice and neonatal encephalopathy and trauma. Hence, Contextualized, 52 locally accepted innovative early neonatal care is crucial to avert the event.

The unknown timing of appropriate initiation of administration has led to controversy over the use of hydrocortisone in the treatment of neonatal sepsis. This study sought to compare the survival rate and NF-κB pathway expression level in newborn mice treated with hydrocortisone at different initiation times after sepsis to find the appropriate administration time window for clinical neonatal sepsis patients. Before building the sepsis model, 36 newborn C57BL/6 mice were randomly divided into six groups with six mice, using quasi-randomization: five treatment subgroups(1 h, 6 h, 12 h, 24 h and 48 h based on the initiation of hydrocortisone therapy) and 1 control group. The survival rate of mice in each group was compared. The expression levels of the NF-κB pathway and inflammatory factors were analyzed and compared among groups. Initiation of hydrocortisone therapy within 12 h of sepsis onset improved the survival of LPS-induced newborn septic mice. Treatment with hydrocortisone over 12 hours reduced the expression level of NF-κB and lowered serum IL-6 and TNF-α levels in cardiopulmonary tissues of mice. Administration of hydrocortisone early in sepsis (within 12 hours) promotes neonatal mouse survival by inhibiting the NF-κB pathway.

Neonatal mortality rates in developing countries are influenced by a complex array of factors. Despite advancements in healthcare, Angola has one of the highest neonatal mortality rates in sub-Saharan Africa, with significant contributors including premature birth, intrapartum events, tetanus, and sepsis. This study aimed to identify the primary causes and contributing factors of neonatal mortality among infants admitted to the Neonatology Service at DBPH in Luanda from May 2022 to June 2023. A retrospective matched case-control design was employed, pairing each neonatal death with two surviving neonates based on age and sex. The analysis included 318 newborns, of whom 106 experienced hospital deaths. A stepwise binary logistic regression model was used to examine associations between variables and neonatal mortality. Variables with p < 0.25 in bivariate analysis were included in the multivariate model. Significant factors associated with neonatal mortality included: a low Apgar score at 1 minute (< 7) (OR 2.172; 95% CI: 1.436–4.731); maternal age under 20 years (OR 3.746; 95% CI: 2.172–6.459); home delivery (OR 1.769; 95% CI: 1.034–3.027); and a short hospital stay of ≤ 48 hours (OR 2.791; 95% CI: 1.183–6.587). Addressing these issues requires urgent interventions, including improving Apgar score management through enhanced training for healthcare professionals, supporting young mothers with intensified maternal education, ensuring deliveries occur in appropriate healthcare settings, and improving universal health coverage and referral systems. These measures could be crucial for enhancing neonatal care and reducing mortality.

The blood that remains in the placenta and umbilical cord after the birth of the infant is referred to as umbilical cord blood (UCB), which has the advantages of convenient source and less ethical controversy. MicroRNA (miRNA) is a class of non-coding RNAs that can regulate gene expression after translation and transcription. Alterations in miRNA expression involve changes in a range of gene expression pathways. An increasing body of research indicates that miRNAs are implicated in many human disorders and are involved in almost all biological medium processes. Due to their high stability in UCB, circulating miRNAs are considered promising biomarkers for diagnosis and disease prognosis. Herein, we conduct a comprehensive review to summarize the roles of diverse UCB miRNAs from different perspectives, including UCB miRNA as biomarker for developmental projections and disease diagnosis, the relationship between maternal gestational status and neonatal UCB miRNA expression, the therapeutic function of exosomal UCB miRNA, miRNA expression profiles in UCB cell lineages. Taken together, miRNAs in UCB are very promising biomarkers for indicating physiological states, disease states, drug responses, development states, or health conditions, which can help in diagnosing, classifying, and predicting diseases, prognosis, or providing personalized treatment plans for patients.

Background: Neonatal transportation of sick newborns is a major predictor of outcome. Prompt identification of the sickest newborns allows immediate corrective intervention and outcome optimization. Multiple severity scores were developed, however an optimal score has not yet been identified. Aim: To identify a rapid, accurate, and easy to perform score predictive for neonatal mortality in outborn neonates. Material and methods: All neonates, irrespective of gestational age, admitted by transfer in our level III regional neonatal unit between 01.01.2015 and 31.12.2021 were included. Infants with congenital critical abnormalities were excluded. Sick neonatal score (SNS) was calculated and compared between survivors and non-survivors. Gestational age (GA), birth weight (BW), gender, Apgar score, place of birth, time between delivery and admission (AT), early onset sepsis were collected from medical records and compared between study groups. Subgroup analysis was performed based on gestational age (preterm versus term infants). A new score was elaborated, including GA, BW, and AT, namely MSNS-AT score, to further improve mortality prediction. The main outcomes were mortality prediction using SNS and MSNS-AT score. Univariable and multivariable analysis, including Cox regression, were performed using SPSS Statistic 22.0. P-value was considered statistically significant if <0.05, 95% confidence intervals, odds ratio and hazard ratios were calculated were appropriate. Results: A total of 418 outborn infants were admitted during study period; 15 infants were excluded due to critical congenital defects. Out of 403 outborn infants, 217 born prematurely (53.8%), 224 males (55.6%), 20 died (4.96%). Compared to the survivors, the non-survivor neonates had significantly lower GA, BW, and SNS score (p<0.05), although only SNS score remained significantly lower in all subgroups (preterm vs term infants). A SNS score ≤8 was associated with mortality both in the whole study group and in subgroups (p<0.001). Time to admission was significantly associated with increased mortality rate in the whole group (p<0.05) and in preterm infants but not in term ones (p>0.05). In univariable and multivariable Cox regression models, MSNS-AT score, with a cut-off optimal value of ≤10 was more precise in predicting mortality compared to SNS (AUC 0.735 vs. 0.775) when applied to the entire group, had a lower accuracy in the term infants (AUC 0.765 vs 0.809) and a better accuracy the preterm infants group (AUC 0.885 vs. 0.810). Conclusions: The MSNS-AT score – calculated by adding GA, BW, and AT to the SNS score - significantly improved mortality prediction at admission in the whole study group as compared to SNS score. The best accuracy prediction of MSNS-AT score was observed in preterm infants suggesting that, besides GA and BW, TA may be decisive for the outcome of outborn preterm infants. Further studies are necessary to confirm the predictive value of MSNS-AT score and to identify variables that can improve its value in term infants without affecting the simplicity, ease, and rapidity of the scoring system.

product transfusions, but clinical practices vary widely. Many very low birth weight (VLBW) infants receive packed red blood cell (RBC) or platelet transfusions during their initial NICU stay, with incidence inversely proportional to gestational age at birth ^1,2. Many critically ill infants are also transfused with plasma or cryoprecipitate to promote coagulation ^3,4. These blood product transfusions are most often prophylactic, with clinical decisions made in response to numerical blood count values, as opposed to therapeutic transfusions in the context of active bleeding.Emerging evidence has shown that some transfusion practices are harmful for certain NICU patients, such as platelet transfusions in preterm infants ^5,6. More broadly, transfusion reactions can occur with virtually all blood products ⁷ and these reactions are likely under-diagnosed, under-estimated, and under-reported in pediatric patients ³. Our intention was to establish optimal transfusion guidelines for our division and neonatal network, including 19 hospitals, based on a review of currently available literature.

Introduction: Parameters used for neonatal mortality calculation vary among publications. Mortality in < 33 weeks gestational age at birth display global variations across different healthcare units. Objective: This study aims to explore trends in neonatal mortality among infants born preterm in the different units in Latin America and the Caribbean utilizing the EpicLatino Network Database in comparison to Canadian Neonatal Network (CNN) 2022. Materials and Methods: This study focused on an eight-year period, with a particular attention to mortality rates during the pre-pandemic (2015-2019) and pandemic/post pandemic (2020-2022) periods. Survival rates from CNN 2022 were included in the comparison analysis. Logistic regression analysis was confined to the 2020-2022 period. Adjustments were made for factors including gestational age, small for gestational age (SGA), Snape II score, inborn/outborn status, and center. As major malformations could account for mortality differences among units. The incidence of major congenital malformations, as defined by CNN, was compared among deceased patients. Results: A total of 15,454 records from 2015-2019 and 10,711 records from 2020-2022 were scrutinized. Overall, there were no significant differences in mortality rates between the two time periods (p=0.22). Moreover, the originating unit during the 2020-2022 period significantly influenced all statistical computations. Conclusions: Survival rates among infants < 26 weeks of gestation in Latin America and the Caribbean are on an upward trajectory, with the healthcare unit playing a pivotal role in this outcome within the EpicLatino database. Major malformations do not seem to be a significant contributing factor. These findings underscore the imperative of implementing quality improvement initiatives to elevate neonatal care standards in Latin America and the Caribbean.

Introduction: In general, everyone believes that the smallest preterm infants should achieve normal intrauterine growth rates, but many thinks that this is not possible with current nutrition guidelines. There is resistance to giving enough nutrition for fear of "toxicity". The difference in weight Z-score between birth and a corrected gestational age (CGA) at discharge is assess in postnatal growth in our unit. Material and methods: An observational study was done between January 2018 and December 2020 where all cases that had ≤ 29 weeks of GA at birth and survived to 36 weeks corrected GA or that were discharged home. An aggressive nutrition protocol including parenteral as well as enteral nutrition was followed. Patients and their weight trajectory was plotted on the Fenton 2013 growth curve. The patients who had had a smaller WZP difference were also plotted. Results: A total of 32 cases were found. The median change in Z-score between birth and discharge of the whole group was -0.52 (IQR 0.53). Six of 32 (19%) had a more than one WZP, all of whom had severe pathologies. The median decline in Z score for this group with poor growth was 1.24 (IQR 0.22). There were 26 cases with a < 1 WZP (81%) and a median Z score fall of 0.39 (IQR 0.55). No important complications secondary to the ingested volumes or parenteral nutrition were reported. Conclusion: The group of cases with a > 1 WZP drop had severe pathologies. All the other cases had adequate growth parallel to normal weight growth charts and a few cases had some catch-up growth. The study showed that it is possible for many preterm infants to achieve normal intrauterine growth rates if they are given enough nutrition, but bigger multicenter studies are needed to confirm these findings.

Neonatal electronic cardiac monitoring in labor and delivery room (DR-ECG) is shown to be sustained at a tertiary care regional perinatal center despite COVID-19 and other complex organizational challenges. In this contemporary cohort, initial increase in chest compressions at birth associated with the introduction of DR-ECG monitoring was mitigated by focused educational interventions on effective ventilation with no difference in neonatal mortality. DR-ECG may help our understanding of human and system factors, identify potential better practices for optimal resuscitation team performance and assess impact of targeted training initiatives on clinical outcomes.

Permanent neonatal diabetes may occur either in isolation or associated with multi-organ syndromes. It is caused by mutations in the genes responsible for pancreatic β cell mass or function. We report new cases of consanguineous parents from Saudi Arabia with a homozygous deletion of exons 1and 2, and exon 5-9 of the GLIS3 gene, who presented with permanent neonatal diabetes associated with intrauterine growth retardation, severe congenital hypothyroidism without other manifestation in the liver, renal or eyes in the 1^st one and cystic renal changes in the 2^nd patient. Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with only 15 reported patients worldwide to date.

Several studies have shown that antibiotics, analgesic – sedative, and antiseizure medications are among the most commonly used medications in preterm and sick neonates. These infants are at high risk of developing nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe, potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. Previous studies and reviews have revealed significant variability in medications used in neonatal intensive care units (NICUs) worldwide, especially concerning the indications and dosages of first-line medications. This variability indicates the lack of adequate studies regarding the effectiveness and safety of these medications in neonates, especially the preterm ones. Important obstacles contributing to inadequate studies in preterm infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the lack of license for use in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials – antifungals, analgesics – sedatives, and antiseizure medications used in neonates, focusing on existing evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage regimen (dose, dosing interval, route of administration), and evidence-based guidelines for the optimal use in neonates.

Neonatal palliative care (NPC) is an integrated and holistic approach that is an integral part of the contemporary neonatal treatment delivery paradigm. It is the highest fulfillment of the notion of beneficence (doing or creating 'good') that has otherwise been neglected/underestimated by the focus of modern medicine on technology and instrumental treatments by its commitment to alleviating patient pain and quality of life. For decades, the Double-Effect Doctrine (DDE) has been used to consider and address a range of ethically questionable circumstances, often at the end of life, including euthanasia, termination of pregnancy to save maternal life, and morally justified warfare. The theory has continued to be mired in controversy as ethicists, legal scholars, theologians, and philosophers discuss the abstract concepts of moral reasoning, purpose, foresight, and other underlying moral theories. In this paper, the moral theory of DDE is discussed in its clinical application to the ethical decision-making process in neonatal palliative and end-of-life treatment, specifically 1) the administration of opioids as required for symptom control and 2) the use of palliative sedation for intractable symptom care.

The literature has addressed the negative impact of poor neonatal conditions (NC) across regions. This has drawn attention to the need to improve NC, particularly in Africa. NC research can make an important contribution. However, there is no study dedicated to this topic in Africa. Through a bibliometric analysis, we arrive at outputs that can inform scientists in planning ongoing or new NC research and those involved in developing and implementing strategies to combat poor NC. Using bibliometrics, the study identified the scientific knowledge on NC between 2000 and 2019, its visibility in the community, the main topics researched, and collaboration patterns.The results show that knowledge on NC has increased between 2000 and 2019, it is concentrated in a few African countries (Egypt, South Africa, Nigeria, Tanzania and Kenya), its visibility is below the world average, in general, maternal mortality is the most researched topic and collaborative activities are frequently, mainly international research collaboration (IRC), being the United States of America (USA) and the United Kingdom (UK) the main partners (they participated in 57% and 28% of all articles with IRC). The collaboration networks are fragile as 43%-67% of all links represent one article in 20 years.Ongoing or new research on NC in Africa should consider the main African players and their partners. There is a need to implement strategies to increase NC knowledge in other African countries, expand and strengthen the collaboration networks and diversify the sources of knowledge.

Background: The rising prevalence of obesity has a significant impact on obstetrics practice regarding maternal and perinatal complications includes recurrent miscarriage, pregnancy-induced hypertension, preeclampsia, gestational diabetes, and prolonged labor. Objective: To assess the impact of obesity on pregnancy and neonatal outcomes among Saudi women. Methods: The study was conducted at King Abdul-Aziz Medical City, Jeddah. Design: A cross-sectional retrospective design. A total number of 186 participants were recruited from July to Dec.2018 according to eligibility criteria. The data were collected retrospectively by a review of the chart records of the labor and delivery department. Results: The mean (SD) age of participants was 31.94(5.67) years old; two-thirds were in obesity class1. There was a significant association between obesity and pre-existing thyroid disease and induced hypertension class3. However, episiotomy showed that obesity class3 was significantly different from obesity class2. Conclusion: This study concludes obesity affects the outcomes of pregnant Saudi associations between obesity and preeclampsia, perineal tears, and episiotomy variables, and other variables reflect no associations. Recommendations: Further studies are needed to generalize the results. This study endorses the pregnant women start the antenatal follow-up from 1st trimester so, the data will be available on the system for research.

The rising prevalence of obesity has a significant impact on obstetrics practice regarding maternal and perinatal complications includes recurrent miscarriage, pregnancy-induced hypertension, preeclampsia, gestational diabetes, and prolonged labor. Objective: To assess the impact of obesity on pregnancy and neonatal outcomes among Saudi women. Methods: The study was conducted at King Abdul-Aziz Medical City, Jeddah. Design: A quantitative research, cross-sectional retrospective design. A total number of 186 participants were recruited from July to Dec.2018 according to eligibility criteria. The data were collected retrospectively by a review of the chart records of the labor and delivery department. Results: The mean (SD) age of participants was 31.94(5.67) years old; two-thirds were in obesity class1. There was a significant association between obesity and pre-existing thyroid disease and induced hypertension class3. However, Episiotomy showed that obesity class3 was significantly different from obesity class2. Conclusion: This study concludes obesity affects the outcomes of pregnant Saudi associations between obesity and preeclampsia, perineal tears, and episiotomy variables, and other variables reflect no associations. Recommendations: Further studies are needed to generalize the results. This study endorses the pregnant women start the antenatal follow-up from 1st trimester so, the data will be available on the system for research.

Background. Candida bloodstream infections (CBSIs) have decreased among pediatric populations in the United States, but remain an important cause of morbidity and mortality. Species distributions and susceptibility patterns of CBSI isolates diverge widely between children and adults. Awareness of these patterns can inform clinical decision-making for empiric or pre-emptive therapy of children at risk for candidemia. Methods. CBSIs occurring from 2006-2016 among patients in a large children’s hospital were analyzed for age specific trends in incidence rate, risk factors for breakthrough-CBSI and death, as well as underlying conditions. Candida species distributions and susceptibility patterns were evaluated in addition to antifungal agent use. Results. The overall incidence rate of CBSI among this complex patient population was 1.97/1,000 patient-days. About half of CBSI episodes occurred in immunocompetent children and 14% in Neonatal Intensive Care Unit (NICU) patients. Antifungal resistance was minimal: 96.7% of isolates were fluconazole-, 99% were micafungin-, and all were amphotericin susceptible. Liposomal amphotericin was the most commonly prescribed antifungal agent including for NICU patients. Overall CBSI-associated mortality was 13.7%; there were no deaths associated with CBSI among NICU patients after 2011. Conclusions. Pediatric CBSI characteristics differ substantially from those in adults. Improved management of underlying diseases and antimicrobial stewardship may further decrease morbidity and mortality from CBSI while continuing to maintain low resistance rates among Candida isolates.

A higher incidence of primary congenital hypothyroidism (CH) has been related to in-creased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the cost-benefit of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n= 162,730; incidence = 1:1,323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical symptoms (p=0.02), lower serum TSH (p

Research studies related to neuroplastic changes that occur secondary to a bout of cystitis at a critical neonatal period of development in female rats (P14-16) are reviewed. They reveal that neonatal bladder inflammation (NBI) leads to an adult phenotype with many of the features of the human disorder, interstitial cystitis. Neurochemical, behavioral and neurophysiological differences between rats which experienced NBI and control animals are discussed and new data presented.

Background: Recent years have seen chaos in the neonatology use of antibiotics with diverse opinions and recommendations in international guidelines and societies. This has created great uncertainty in which cases to use, for how long, and which tests apply to make these decisions. We conducted a retrospective cohort study about the use of antibiotics in the EpicLatino neonatal units and a Latin American network database, after noting these variations in the 2019 report. Methods: For the year 2019 using the EpicLatino database, we included cases (only first admission) ≤32 weeks gestational age at birth, excluding one unit that did not accept to participate. The number of cases and days receiving antibiotics were recorded as well as the progression for each unit. Inappropriate use of antibiotics was defined as greater than 3 days in patients with negative cultures (blood/CSF cultures) excluding: major malformations, urinary tract infections, necrotizing enterocolitis (NEC) and cases with suspected chorioamnionitis in the mother (the latter two only during the course of diagnosis of NEC or chorioamnionitis). This study was approved by the EpicLatino board of directors and by the participating units. Results: A total of 6,543 days of antibiotics were observed, 49.5% of cases had at least one positive blood/CSF culture. A total of595 days of antibiotics without justification were found in 72 courses in 61 cases; 14/72(19.4%) had no diagnosis of infection in the database, 7/72(9.7%) did not document any culture throughout their stay, and 37/72(51,4%) obtained only one blood/CSF culture during their entire stay. Most diagnosis were clinical sepsis and in 24/58(41%) curses, a diagnosis of pneumonia with a poor positive culture correlation was found. Furthermore, 74% of the units didn´t use pneumonia as a justification to use antibiotics. Other diagnosis found: Conjunctivitis, NEC 1A and rotavirus NEC. Conclusions: Although the method of reviewing the use of antibiotics in a database has a number of limitations, especially the cause that motivated the use of antibiotics and other tools used for diagnosis of infections, the notable differences between units is striking. Although it is difficult to make recommendations to all units, it is important to control infections in some units and in others to reduce the excessive use of antibiotics, especially with diagnosis of pneumonia in neonates and negative blood/CSF cultures.

1) Introduction: Brain parcellation is an important processing step in the analysis of structural brain MRI. Existing software implementations are optimized for fully developed adult brains, and provide inadequate results when applied to neonatal brain imaging. 2) Methods: We developed a semi-automated pipeline, NeBSS, for extracting 50 discrete brain structures from neonatal brain MRI, using an atlas registration method that leverages the existing ALBERT neonatal atlas 3) Results: We demonstrate a simple linear workflow for neonatal brain parcellation. NeBSS is robust to variation in imaging acquisition protocol and magnet field strength. 4) Conclusion: NeBSS is a robust pipeline capable of parcellating neonatal brain MRIs using a simple processing workflow. NeBSS fills a need in clinical translational research in neonatal imaging, where existing automated or semi-automated implementations are too rigid to be successfully applied to multi-center neuroprotection studies and clinically heterogeneous cohorts. The software is open source and freely available.

Neonatal sepsis is a leading cause of morbidity and mortality in neonates, particularly in low and middle-income countries. The emergence of antimicrobial resistance is a rapidly growing global problem. A significant proportion of the pathogens that commonly cause neonatal sepsis are resistant to multiple antibiotics. Therefore, for the empirical treatment of neonatal sepsis, the repurposing of older antibiotics that are effective against multidrug-resistant pathogens is being investigated. This review aims to provide an overview of current research and experience using the repurposed antibiotics, Colistin and Fosfomycin, for the empirical treatment of neonatal sepsis. Based on current knowledge, Colistin and Fosfomycin may be potentially helpful for the empirical treatment of sepsis in neonates due to their efficacy against a wide range of pathogens and acceptable safety profile.

Background: During the stay in the neonatal intensive care unit, parents play a crucial role in the care of their infants. Recent studies reported a decrease in parental participation due to Coronavirus Disease (COVID-19) pandemic that determined restricted access policies in hospitals. The aim of this study is to describe the barriers to a good parents’ participation during the stay in the neonatal intensive care unit in the COVID-19 era. Methods: A quantitative observational study was carried out. Results: 270 parents participated in this study. Mothers’ participation in care seems to be higher as compared to fathers (p = 0.017). Parents who lived the birth of their first child reported a better level of participation in care when compared to those who lived the birth of their second born (p = 0.005). Parents of extremely preterm neonates reported a lower interaction with their infant if compared to parents of term newborns (p &lt; 0.001). Conclusions: Some more disadvantaged categories have reported lower scores: cultural and linguistic minorities, parents of multiple children and fathers. COVID-19 pandemic made several Family Centred Care activities not possible with a higher impact on those who benefited the most of these facilities. This study was prospectively registered by the IRB-CRRM of the University “G. d’Annunzio” Chieti-Pescara on the 23/01/2024 with registration number CRRM;2023_12_07_01.

The COVID-19 pandemic has raised concerns about its impact on maternal and neonatal health. This study aimed to investigate the influence of maternal COVID-19 infection during pregnancy on neonatal inflammatory parameters. A retrospective cohort study was conducted at Premiere Hospital in Timisoara between May 2021 and January 2022. Participants were categorized into two groups: the COVID-19 positive group, consisting of patients with confirmed SARS-CoV-2 in-fection during pregnancy, and the control group, which comprised COVID-19-free pregnant women. The primary outcome was the assessment of inflammatory markers (NLR, dNLR, PLR, and SII) in neonates born to mothers with COVID-19. The results suggest that maternal COVID-19 infection during pregnancy significantly impacts certain neonatal inflammatory parameters. Spe-cifically, newborns exposed to maternal COVID-19 exhibited elevated white blood cell counts, particularly when infection occurred during the first trimester. Lymphocyte counts were dimin-ished in neonates born to COVID-19-positive mothers, irrespective of infection trimester. Gesta-tional age played a role in altering neonatal immune profiles, with correlations observed between GA and parameters in the Control Group (COVID-19 negative during pregnancy). However, the influence of neonatal immunoreactivity on laboratory parameters remained generally non-significant after adjusting for GA and infection trimester. In conclusion, maternal COVID-19 infection during pregnancy has a discernible impact on neonatal inflammatory parameters, in-cluding WBC and lymphocyte counts, which may have clinical implications.

Abstract: Objective: We aimed to look for the mortality of Black and White Neonates and compare the Black and White neonates' mortalities after stratifying the population by many significant epidemiologic and hospital factors. We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA. Design/Method: We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA. Neonatal characteristics used in the analysis included ethnicity, sex, household income, and type of healthcare insurance. Hospital characteristics were urban teaching, urban non-teaching, and rural. Hospital location was classified according to the 9 U.S. Census Division regions. Results: Neonatal mortality continues to be higher in Black: 21,975 (0.63%) and in White was: 35495 (0.28%), Government-supported health insurance was significantly more among Black populations when compared to White (68.8% vs. 35.3% p<0.001). Household income differed significantly; almost half (49.8%) of the Black population has income ≤ 25th percentile vs. 22.1% in White. There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division (0.72%), and the lower mortality was in the New England division (0.51%), whereas in the White population, the highest mortality was in the East South-Central division (0.36%), and the lowest mortality was in the New England division (0.21%). Trend analysis showed a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by sex, types of insurance, the household income, the type of hospitals, the mortality was consistently higher in Black groups throughout the study years, Conclusions: Disparities in neonatal mortality continue to be higher in Black; There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division, and the lower mortality was in the New England division, whereas in the White population, the highest mortality was in the East South-Central division, and the lowest mortality was in the New England division. There has been a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by many significant epidemiologic and hospital factors, the mortality was consistently higher in Black groups throughout the study years.

Neonatal drug information (DI) is essential for safe and effective pharmacotherapy in (pre)term neonates. Such information is usually absent from drug labels, making formularies a crucial part of the neonatal clinician’s toolbox. Several formularies exist worldwide, but they have never been fully mapped nor compared for content, structure and workflow. The objective of this review was to identify neonatal formularies, explore (dis)similarities, and raise awareness of their existence.Neonatal formularies were identified through self-acquaintance, experts and structured search. A questionnaire was sent to all identified formularies to provide details on formulary function. An original extraction tool was employed to collect DI from the formularies on the 10 most commonly used drugs in pre(term) neonates.Eight different neonatal formularies were identified worldwide (Europe, USA, Australia-New Zealand, Middle East). Six responded to the questionnaire and were compared for structure and content. Each formulary has its own workflow, monograph template and style, and update routine. Focus on certain aspects of DI also varies, as well as the type of initiative and funding.Clinicians should be aware of the various formularies available and their differences in characteristics and content to use them properly for the benefit of their patients.

Congenital deafness is a major pediatric problem, affecting about 1.5-3 per 1000 newborns. The early treatment through cochlear implantation and auditory rehabilitation has been a historic milestone. Early diagnosis of congenital deafness is an essential requirement to obtain the best results, which is achieved through neonatal screening, a diagnostic practice that we began systematically at the Hospital Clínico in Valencia (Spain) 30 years ago.

Annually, an estimated 13-26 million newborns need respiratory support and 2-3 million newborns need extensive resuscitation, defined as chest compression and 100% oxygen with or without epinephrine in the delivery room. Despite such care, there is a high incidence of mortality and short-term neurologic morbidity. The poor prognosis associated with receiving chest compression alone or with medications in the delivery room raises questions as to whether improved cardiopulmonary resuscitation methods specifically tailored to the newborn could improve outcomes. This review discusses the current recommendations, mode of action, different compression to ventilation ratio, continuous chest compression with asynchronous ventilations, chest compression and sustained inflation optimal depth, and oxygen concentration during cardiopulmonary resuscitation.

Harms of combustible cigarette (CC) use in pregnancy for fetal development are well-studied. Less understood is potential impacts of newer non-combustible cigarette alternatives, including electronic cigarettes (EC). Our goal was to examine whether EC use during pregnancy predicts increased risk of adverse birth outcomes. This retrospective cohort study used data from the Obstetrics Initiative (OBI), a statewide collaborative of 70 maternity hospitals. OBI’s clinical registry of data on nulliparous, term, singleton, vertex fetal presentation pregnancies were from medical records. Three groups of pregnancy cigarette users (Controls (n=26,394), CC (n=2,216), EC (n=493) were compared on birth outcomes, controlling for background differences. Compared to controls, the EC group had significantly lower birth weight, while CC had reduced birthweight and greater rates of arterial cord pH < 7.1. Compared to EC, CC users had higher rates of neonates requiring antibiotics and NICU admission. Growing evidence suggests EC are not safer alternatives to CC, and use during pregnancy should be discouraged. Additional research is needed, as non-significant trends for increased risk of several adverse neonatal outcomes following EC use were found, potentially significant in larger studies with average-risk for adverse pregnancy outcomes and when frequency and timing of EC exposure are considered.

Invasive Candida infections represent a significant cause of morbidity and mortality in the neonatal intensive care unit (NICU), particularly among preterm and low birth weight neonates. The nonspecific clinical presentation of invasive candidiasis, resembling that of bacterial sepsis with multiorgan involvement, makes the diagnosis challenging. Given the atypical clinical presentation and the potential detrimental effects of delayed treatment, empirical treatment is often initiated in cases with high clinical suspicion. This underscores the need to develop alternative laboratory methods other than cultures, which are known to have low sensitivity and a prolonged detection time, to optimize therapeutic strategies. Serum biomarkers, including mannan antigen/anti-mannan antibody and 1,3-β-D-glucan (BDG), both components of the yeast cell wall, a nano-diagnostic method utilizing T2 magnetic resonance and Candida DNA detection by PCR-based techniques have been investigated as adjuncts to body fluid cultures and have shown promising results in improving diagnostic efficacy and shortening detection time in neonatal populations. This review aims to provide an overview of the diagnostic tools and the current management strategies for invasive candidiasis in neonates. Timely and accurate diagnosis followed by targeted antifungal treatment can significantly improve the survival and outcome of neonates affected by Candida species.

Invasive Candida infections represent a significant cause of morbidity and mortality in neonatal intensive care units (NICUs), with a particular impact on preterm and low birth weight neonates. In addition to prematurity, several predisposing factors for Candida colonization and dissemination during NICU hospitalization have been identified, including prolonged exposure to broad-spectrum antibiotics, central venous catheters, parenteral nutrition, corticosteroids, H2 antagonist administration and poor adherence to infection control measures. According to the literature, the implementation of antifungal prophylaxis, mainly fluconazole, in high-risk populations has proven to be an effective strategy in reducing the incidence of fungal infections. This review aims to provide an overview of risk factors for Candida invasive infections and current perspectives regarding antifungal prophylaxis use. Recognition and reduction of exposure to these modifiable risk factors, in conjunction with the administration of antifungal prophylaxis, has been demonstrated to be an effective method for preventing invasive candidiasis in susceptible neonatal populations.

The use of antibiotics in neonatal units worldwide varies significantly. We included data from 2015-2022 from the EpicLatino database, which comprises a network of 32 units in Latin America and the Caribbean with gestational age at birth (GA) of ≤ 32 weeks. A questionnaire was sent to the EpicLatino units, to correlate practice with outcomes. Negative binomial regression with standard errors and confidence intervals computed for incidence-rate ratios (IRRs) was used for comparative statistics on antibiotic days per 1000 patient-days between units. All units that responded had 1-6 differences with the reference unit (Unit 2) with the best results, but there was no clear association with the IRR. Each EpicLatino unit should review its statistics to explore possibilities for reducing antibiotic usage.

The field of human microbiome and gut microbial diversity research has witnessed a profound transformation, driven by advances in omics technologies. These advancements have unveiled essential connections between microbiome alterations and severe conditions, spurring the development of new frameworks through epidemiological studies. Traditionally, each individual was thought to harbor unique microbial communities acquired early in life, but recent research challenges this belief. The neonatal microbiome's onset, influenced by factors like delivery mode and maternal health, remains a subject of intense debate, hinting at potential intrauterine microbial processes. In-depth research reveals associations between microbiome profiles and specific health outcomes, ranging from obesity to neurodevelopmental disorders. Understanding these diverse microbiome profiles is essential for unraveling the intricate relationships between the microbiome and health outcomes.

Background: Neonatal cholestasis (NC) initiates in the first trimester of a newborn, comprising extra and intrahepatic medical conditions, with a high risk of fatality warranting early diagnosis and treatment to prevent morbimortality. The differential diagnosis of NC is a challenge demanding an accurate diagnosis for disease detection. The current study evaluates NC's clinical symptoms and differential diagnosis using ultrasound, liver biopsy, histopathology, and biochemistry. Methods: Infant registry data from Hevi Pediatric Teaching Hospital (January 2016 - January 2022) were obtained and screened for subject selection. The inclusion criteria include infants with direct hyperbilirubinemia within an onset of 1 to 90 days of birth. As indicated, the recruited subjects underwent liver ultrasound, blood biochemistry, and liver biopsy. Results: Seventy-two children presented with the criteria for inclusion in the study. The study found that ultrasound helped diagnose 43.1% of subjects for BA compared to 34.7% through histopathology. The histopathology confirmed 13 children (18.1%) having neonatal hepatitis. Test sensitivity of the ultrasound method for BA and NH was 60% (40.74, 76.6) and 38.46% (17.71, 64.48), respectively. Conclusion: The study found both ultrasound and liver biopsy to be critical diagnostic methods to differentiate the etiology of NC. Ultrasound has a higher specificity and sensitivity for diagnosing BA than NH. Histopathology and blood biochemistry should be considered, too, for effective diagnosis. In the future, larger sample and multicenter studies should be conducted to develop practically implementable strategies.

Background Obesity compromises the health of a woman's pregnancy and her newborn. Aim: To describe weight-gaining changes throughout pregnancy and evaluating outcomes for the mother and the baby. Methods A retrospective review of women who delivered singletons using Large Perinatal Registry. According to their BMI, patients were categorized into four categories: underweight, normal, overweight, and obese. Mode of delivery, gestational diabetes, hypertensive diseases, obstetric cholestasis, and postpartum hemorrhage were the main maternal outcome measures. The newborn outcome indicators were birth weight, NICU hospitalization, premature birth, and stillbirth. Results The study sample included 2,352 natives (25%) and 7,058 expatriates (75%). The majority of the sample (4726) were aged 20-29 years, 43.6% were aged 30-39 years, and 2.1% and 3.9% were aged 19 years and 40 years respectively. The incidence of hypertension, obstetric cholestasis, diabetes, postpartum hemorrhage, and cesarean section varied among the entire sample. In the underweight group, the incidence of CS was 15.7%, in the normal weight group (24.9%), in the overweight group (31.3%), and in the obese group (41%). Hypertensive disorders were 3 times more prevalent in obese women than in normal-weight women (2%), and 5.3% of obese women had PPH compared to 5. 6% of women of normal weight. The underweight groups gained the most weight during pregnancy, whereas the obese gained the least. Conclusions A significant proportion of pregnant women in our sample will become obese by the time of delivery. Obesity during pregnancy is associated with negative maternal and fetal outcomes.

The aim of the study was to determine the maximum safe concentration of calcium and phosphate in neonatal parenteral nutrition (PN) solutions when various combinations of inorganic and organic salts are applied. Twelve PN solutions for neonatal use were aseptically prepared. Increasing concentration of inorganic and organic calcium and phosphate were added to the standard formulas. Each admixture was separately tested according to following conditions; after mixing, 37°C for 24 h, and maximum safe combination of calcium and phosphate were stored at 4°C for 30 days and followed by 24 h at 37°C. Visual inspections against a black and white contrast background, microscopic observation of undiluted PN solutions as well as the membrane filter after filtration of the PN solution, pH evaluation, and spectrophotometry at 600 nm were examined in triplicate. Safe maximum concentration of organic and inorganic calcium and phosphate was proposed individually for each composition of parenteral nutrition solutions. Surprisingly organic calcium with organic phosphate showed precipitation but over the therapeutic range. The protective effect of amino acid was observed and higher concentrations of calcium and phosphate were free of precipitation.

Background-Bronchopulmonary dysplasia (BPD) is a condition of poor alveolar formation that causes chronic breathing impairment in infants born prematurely. Preterm lungs lack surfactant and are vulnerable to oxidative injuries driving the development of BPD. Our recent studies reported that surfactant protein A (SP-A) genetic variants influence susceptibility to neonatal lung disease. SP-A modulates activation of alveolar macrophages and parturition onset in late gestation. We asked whether a lack of SP-A alters alveolarization in a mouse model of hyperoxia-induced BPD. Methods- SP-A-deficient and control newborn mice were exposed to either clinically relevant 60% O2 hyperoxia or normoxia for 5-7 days. Alveolar formation was then assessed by mean linear intercept (MLI) and radial alveolar count (RAC) measurements in lung tissue sections. Results- We report that the combination of SP-A deficiency and hyperoxia reduces alveolar growth compared to WT mice. The morphometric analysis of normoxic SP-A-deficient lungs showed lower RAC compared to controls, indicating reduced alveolar number. In the presence of hyperoxia, MLI was higher in SP-A-deficient lungs compared to controls. Differences were statistically significant for female pups. Spatial proteomic profiling of lung tissue sections showed that hyperoxia caused a 4-fold increase in the DNA damage marker gammaH2Ax in macrophages of SP-A-deficient lungs compared to normoxia. Conclusions- Our short report suggests an important role for SP-A in perinatal lung development and in protecting lung macrophages from oxidant injury. These studies warrant future investigation to discern the temporal interaction of SP-A, gender, oxidant injury, and lung macrophages in perinatal alveolar formation and development of BPD.

Complexity of care, adequate staffing levels, and workflow are key factors affecting nurses’ workloads. Clinical complexity classification and related staffing adjustment remain notable gaps in the current evidence limiting the capacity for optimal staffing practices. This study aimed to adapt and validate the WANNNT-SC to the Italian context to allow the assessment of newborns admitted to the NICUs. To evaluate the reliability of the tool among different profes-sionals, a correlation test was performed using Pearson’s correlation, which resulted in a strong correlation (r = 0.967, p = 0.01). In the test-retest phase, there was a significant correlation (r = 0.910 and p = 0.01). Using an analysis of variance, we found that the higher the I-WANNNT-SC score, the higher the predicted death rate (F = 13.05 and p < 0.001). The Italian Winnipeg Surgical Complex Assessment of Neonatal Nursing Needs Tool represents the first tool available for the Italian context that aims to measure the nursing workload in neonatal intensive care. It could allow adjustments in nursing staffing based on NICU activities and patient needs. This study was prospectively approved by the local Ethics Committee “Palermo 1” (Protocol CI-NICU-00).

Vitamin D deficiencies are very common in pregnant women, raising concerns about adverse health outcomes in children. This issue has hardly been studied in multiple pregnancies, the prevalence of which has been steadily increasing. Therefore, our study investigated the relationship between newborns’ anthropometric parameters and the concentration of 25(OH)D in maternal blood of women with twin pregnancies and umbilical cord blood. The study included 50 women who gave birth after the 36th week of twin gestation. 25(OH)D was determined in maternal blood collected during the antenatal period and in the umbilical cord blood of 100 newborns. Anthropometric parameters of the newborns (birth weight, length, head and chest circumference) were obtained from hospital records. Data on nutrition and lifestyle during pregnancy were collected from the patients during an interview conducted by a dietitian. No relationship between maternal and neonatal cord blood vitamin D concentrations and any of the anthropometric parameters of the newborns was found. However, only 6% of the mothers and 13% of the newborns had vitamin D deficiency (≤20 ng/mL). The type of pregnancy and maternal height were the main factors associated with neonatal size. Newborns from dichorionic pregnancies were on average 202 g heavier (p<0.001) and 1 cm longer (p=0.006) than newborns from monochorionic pregnancies. Newborns of mothers ≤ 160 cm in height had on average 206 g lower birth weight (p=0.006) and were 3.5 cm shorter (p=0.003) compared to newborns of taller mothers. Therefore, in our study, neonatal size of the twins was not related to the vitamin D status but to other factors such as the type of pregnancy and maternal height.

The architectural configuration of the space plays a crucial role in the acoustics of Neonatal Intensive Care Units (NICUs). The design of the environment, the materials used in construction, and the organisation of noise sources within the room significantly influence the noise levels present in these critical areas. For this research, noise levels found in two hospitals, with different architectural configurations and sizes but similar construction materials, have been analyzed. Data were recorded at 1-second intervals over a period of more than 24 hours. The data collected in these hospitals confirm the magnitude of the noise problem in NICUs, highlighting the urgent need to address it effectively to ensure an appropriate and safe environment for the recovery of neonates. Good architectural planning can help mitigate noise, while poor configuration can exacerbate acoustic problems, negatively affecting both patients and healthcare staff. It is crucial to involve architects, acoustic engineers, and healthcare staff in the design and renovation of NICUs to create spaces that not only meet medical needs but also consider the auditory well-being of neonates.

Human milk (HM) feedings are associated with reduced risks of neurodevelopmental and neurocognitive delays and systemic inflammatory diseases in infants born prematurely and/or at a low birth weight. Utilizing a neonatal piglet model, HM feedings were compared to bovine milk-derived infant formula (IF)-feedings with the aim of understanding the underlying mechanisms involved in reducing these risks. Six male piglets at postnatal-day (PD)2 were randomized into two feeding groups: HM-fed (n = 3) or IF-fed (n = 3) for 28 days. At 3- and 4-weeks-old, piglet memory and learning performance were assessed using novel object recognition (NOR). At PD30 piglets were euthanized, and whole brains were excised, weighed, and preserved for further analyses, and brain microglial morphology, and systemic inflammatory cytokines were quantified. During NOR, HM-fed piglets had significantly more non-novel revisits at both 3- and 4-weeks-old compared to IF-fed piglets. Microglia of HM-fed piglets had longer processes, more branch points, more endpoints, and a larger territorial volume compared to IF-fed piglets at PD30. In a neonatal piglet model, HM-feedings may improve cognition and reduce brain inflammatory response compared to IF-feedings.

Background: Survival and outcome of extremely preterm (EP) infants have improved due to changes in the management of stabilization at birth and respiratory distress syndrome. Methods: In a retrospective study conducted at an academic perinatal level III center in Romania, we compared the effects of different protocols on the early outcomes of EP infants of two different periods (2008-2012 vs. 2018 vs. 2022). Two subgroups were studied in each period, based on gestational age (GA), 22-25 weeks, and 26-28 weeks, excluding those with significant congenital anomalies or missing data. Results: 270 EP infants were included in the study (121/149), with a mean GA 26.1±1.6/26.7±1.1 weeks. Significant improvements were found during period II regarding initial FiO2 (40% vs. 100%; &lt;0.001), nCPAP (55.7% vs. 19.0%; p&lt;0.001) at birth, early rescue surfactant administration (65.8% vs. 34.7%; p&lt;0.001), need of mechanical ventilation (58.4% vs. 98.3%; p&lt;0.001). Survival rates of EP infants significantly improved from 41.3% to 72.5%, particularly in the 26-28 weeks subgroup (63.8% to 83%). The frequency of severe IVH decreased in period II from 30.6% to 14.1%, while the rates of BPD were lower in period II (23.4% vs. 36.6%; p=0.045), in the 26-28 weeks subgroup. We found improvements but no significant differences in NEC, sepsis, PVL, ROP, or PDA frequencies. Conclusions: Using updated guidelines and protocols is crucial for improving outcomes.

Second-level hospitals face peculiarities that hinder the implementation of the hearing rescreening protocol, which are not uncommon in other settings. This study analyzes the hearing rescreening process in this kind of hospital. A total of 1130 individuals were included. In this cohort, 61.07% were newborns in the hospital who failed their first otoemission test after birth (n=679) or were unable to have the test performed (n=11), then being referred to outpatient clinic. The remaining 38.93% were individuals who were born in another hospital with their first test conducted in the outpatient clinic (n=440). A high amount of rescreenings were made outside the recommended time frame, mainly in children referred from another hospital. There was a high rate of lost to follow-up especially with otolaryngologist referrals. Neonatal Hearing screening in second level hospitals is difficult because of the staffing and time constraints. This results in longer than recommended turnaround times and interferes with the timely detection of hearing loss. This is particularly serious in outpatients. Referral of children with impaired screening to out-of-town centers leads to unacceptable loss of follow-up. A legislative support for all these rescreening issues is necessary. We discuss these findings and propose some solutions.

Increasing evidence suggests that prenatal exposure to opioids can adversely influence brain development, yet, limited data exists on the effects of opioid-exposure on preschool language development. Our study aimed to characterize the nature and prevalence of language problems in children prenatally exposed to opioids, and the factors that support or hinder language acquisition. A sample of 100 children born to pregnant women in methadone maintenance treatment and 110 randomly identified non-exposed children were studied from birth to age 4.5 years. At 4.5 years, 89 opioid-exposed and 103 non-exposed children completed the preschool version of the Clinical Evaluation of Language Fundamentals (CELF-P) as part of a comprehensive neurodevelopmental assessment. Children prenatally exposed to opioid had poorer receptive and expressive language outcomes at age 4.5 years compared to non-exposed children. After adjustment for child sex, maternal education, other pregnancy substance use, maternal pregnancy nutrition and prenatal depression, opioid exposure remained a significant independent predictor of children’s total CELF-P language score. Examination of a range of potential intervening factors showed that a composite measure of the quality of parenting and home environment at 18 months and early childhood education participation at 4.5 years were important positive mediators.

In pigs, iron deficiency anemia (IDA) is the most prevalent deficiency disorder during the early postnatal period frequently developing into a critical illness. Meanwhile, in humans, only low-birth-weight infants, including premature infants are especially susceptible to developing IDA. In both human and pig neonates, the initial cause of IDA is low birth iron stores. In piglets this shortage of stored iron results mainly from genetic selection over the past few decades for large litter size and high birth weight. In consequence, pregnant sows cannot provide sufficient amount of iron to the increasing number of developing fetuses. Supplementation with iron is a common practice for the treatment of IDA in piglets. For decades, the preferred procedure for delivering iron supplements during early life stages has been through the intramuscular injection of large amount of iron dextran. However, this relatively simple therapy, which in general, efficiently corrects IDA, may generate toxic effects, and by inducing hepcidin expression, may decrease bioavailability of supplemental iron. New iron supplements are considered now with the aim to combine improvement of hematological status, blunting hepcidin expression, and minimizing toxicity of the administered iron. We propose that iron-deficient piglets constitute a convenient animal model for performing pre-clinical studies with iron supplements.

Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure-activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24-h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

The fetal splenic artery pulsatility index (PI) is a parameter that reflects fetal well-being and has been used as a predictor of adverse pregnancy outcomes. The aim of this study was to investigate the predictive value of splenic artery PI in GDM class A1 cases for NICU admission. In this prospective case controlled study, only sixty single pregnancy cases diagnosed with gestational diabetes mellitus class A1 were evaluated. Fetal splenic artery Doppler parameters Peak systolic velocity (PSV), Pulsatility index (PI), Resistivity index (RI) and End diastolic velocity (EDV) were measured in all cases. The rate of re-quirement of need of neanoatal intensive care unit was noted. In cases with need fetal intensive care, fetal splenic PI index was found to be statistically significantly lower than in healthy cases without it (0.94 ± 0.29 vs. 1.70 ± 0.53, respectively, p

Neonatal disorders, particularly those resulting from prematurity, pose a major challenge to health care and have a significant impact on infant mortality and long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer a compelling opportunity for neonatal therapy by harnessing the inherent regenerative capabilities of EVs. These nanoscale particles, secreted by a variety of organisms including animals, bacteria, fungi and plants, contain a repertoire of bioactive molecules with therapeutic potential. This review aims to provide a comprehensive assessment of the therapeutic effects and mechanistic insights of EVs from stem cells, biological fluids and non-animal sources, with a focus on common neonatal conditions such as hypoxic-ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis. This review summarizes the evidence for the therapeutic potential of EVs, analyzes the evidence on their mechanisms of action, and discusses the challenges associated with the implementation of EV-based therapies in neonatal clinical practice.

Information on the effect of bloody amniotic fluid during labor at term is scarce. This study assessed risk factors and obstetrical outcomes in labors complicated by bloody amniotic fluid. All nulliparas with singleton pregnancy, who underwent a trial of labor ≥37 weeks of gestation, in a single tertiary center, over six years were included. Obstetrical, delivery and neonatal outcomes were compared between deliveries with bloody amniotic fluid or clear amniotic fluid. Overall, 11,252 women were included. Among them, 364 (3.2%) had bloody amniotic fluid and 10,888 (96.7%) had clear amniotic fluid. Women with bloody amniotic fluid were characterized by shorter duration of the second stage of labor and higher rate of cesarean delivery due to non-reassuring fetal heart rate. The rates of cord pH &lt; 7.1 and NICU admissions were also higher. In multivariate logistic regression analysis, cesarean delivery, cord blood pH &lt; 7.1 and NICU admission were independently associated with increased odds ratio for bloody amniotic fluid. Bloody amniotic fluid at term is associated with adverse outcomes and must be considered during labor.

Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalizations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.

Pemphigus vulgaris is an autoimmune blistering disease of the epidermis, caused by autoantibodies against desmosomal proteins, mainly desmogleins 1 and 3, which induce an impairment of desmosomal adhesion and blister formation. Recent findings have shown that inhibition of immunoglobulin G binding on the neonatal Fc receptor, FcRn, results in reduced autoantibody recycling and shortens their half-life, providing a valid treatment option for PV. We have here analyzed the role of FcRn in human keratinocytes treated with novel, recombinant anti-desmoglein-3 antibodies that induce pathogenic changes in desmosomes, such as loss of monolayer integrity, aberrant desmoglein-3 localization and degradation of desmoglein-3. We show that blocking IgG binding on FcRn by efgartigimod, a recombinant Fc fragment that is undergoing clinical studies for pemphigus, stabilizes the keratinocyte monolayer, whereas the loss of desmoglein-3 is not prevented by efgartigimod. Our data show for the first time that FcRn may play a direct role in the pathogenesis of pemphigus at the level of the autoantibody target cells, the epidermal keratinocytes. Our data also imply that in keratinocytes, FcRn may have functions different from its known function in IgG recycling. Therefore, stabilization of keratinocyte adhesion by FcRn blocking entities may provide a novel treatment paradigm for pemphigus.

Our previous study demonstrated that the acute high-dose rate (3.3 Gy/minute) gamma irradiation of postnatal day 3 (P3) mice with 5Gy induced depression and drastic neuropathological changes in the dentate gyrus of the hippocampus of the adult mice. The present study investigated the effects of chronic low-dose-rate (1.2mGy/h) gamma irradiation from P30 to P180 with a cumulative dose of 5Gy on animal behaviour, hippocampal cellular change, miRNA and mRNA expression in the hippocampus and blood in female mice. The radiation exposure did not significantly affect the animal's body weight and neuropsychiatric changes such as anxiety and depression examined by neurobehavioural tests including open field, light-dark box, elevated plus maze, tail suspension test and forced swim test. Immunohistochemical staining did not detect any obvious loss of mature and immature neurons (NeuN and DCX) or any inflammatory glial response (IBA1, GFAP, and PDGFR1). Nevertheless, r-H2AX foci in the stratum granulosum of the dentate gyrus were significantly increased, suggesting the chronic low dose rate irradiation induced persistent DNA damage foci in mice. miRNA sequencing and qRT-PCR indicated an increased expression of miR-448-3p and miR-361-5p, but decreased expression of miR-193a-3p in the mouse hippocampus. Meanwhile, mRNA sequencing and qRT-PCR showed a reduced expression of Ccn1, Fli1, Fosb, Ets1, Hs3st5, and Eif4ebp1, but enhanced expression of Cort, Foxh1, and Opalin. Database searching by miRDB and TargetScan predicted that FLI1 and HS3ST5 are the targets of miR-448-3p, and Eif4ebp2 is the target of miR-361-5p. miRNA/mRNA sequencing and qRT-PCR results in blood showed the increased expression of miR-6967-3p and the decreased expression of its target S1pr5. The interactions of these miRNAs and mRNAs may contribute to the chronic low dose rate radiation-induced persistent DNA damage.

Early discharge after childbirth has led to a rise in neonatal readmission, becoming a major concern in recent decades. Our research aimed to identify the risk factors and incidence of neonatal readmission, as well as explore preventive measures. Our study at the Clinical Hospital of Pediatrics in Ploiești, Romania included 108 neonates admitted during the neonatal period. This accounted for 2.06% of all admissions (5226). The most prevalent cases were malnutrition (25%), fever (20.3%) and bronchiolitis (17.5%). Diarrhea and infectious gastroenteritis were also observed (14.8%), along with acute rhinoconjunctivitis (9.2%) and late onset sepsis (3.7%). No deaths were recorded. The most significant characteristics identified were number of children (p&lt;0.001) and age at maternity discharge (p&lt;0.001). By following the prevention rules, malnutrition, feeding errors, and infections can be avoided. This includes practicing proper hand hygiene for both mothers and medical staff, as well as educating and demonstrating to mothers the benefits of breastfeeding. In addition, all newborns discharged from the maternity ward should benefit from follow-up at 7-10 days of life. Our results confirm the effectiveness of a multidisciplinary team and endorse promoting breastfeeding. Implementing quality control measures and regularly evaluating the surveillance program will help improve its effectiveness.

(1) Background: To estimate resistance, reactance and phase angle values among moderate preterm infants and their variation according to neonatal and maternal characteristics and nutritional intake. (2) Methods: This was a cohort that evaluated 43 moderate preterm infants using bioelectrical impedance analysis. The study variables included resistance, reactance and PA measurements, in addition to classification of nutritional intake. (3) Results: The mean resistance was 602.0+118.2 Ω, reactance was 57.2 Ω (IIQ = 42.6-65.2) and phase angle was 522° (IIQ = 4.1-6.6). Lower resistance values were found in the presence of risky pregnancy (532.2+111.9 Ω vs 650.9+97.9 Ω, p&lt;0.001) and lower reactance values, in the presence of harmful maternal lifestyle habits at both the first (p=0.01) and second assessments (p=0.01). Eight preterm infants were considered to have insufficient nutritional intake (23.5%); 17, sufficient (50.0%) and 9, partially sufficient (26.5%). There was less reactance among preterm infants with insufficient nutritional intake (p &lt; 0.001). (4) Conclusions: The bioelectrical impedance analysis measurements were within the range of values reported in other studies. There was an association between full diet and adequate nutritional intake with higher resistance values, and a lower reactance value was associated with the presence of risky pregnancy and harmful maternal lifestyle.

Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to treat with hypothermic therapy is critical. Differentiating HIE from other neonatal conditions, such as sepsis, further complicates the diagnosis. This study investigated the utility of a metabolomic-based approach using the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice-Vannucci model of HIE in rats. We evaluated the diagnostic accuracy of this method between 3 and 6 hours after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic accuracy with areas under the curve (AUC) of 0.94 at 3 hours and 0.96 at 6 hours after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 hours of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.

Early onset neonatal sepsis is a significant contributor to neonatal morbidity and mortality. Although blood cultures remain the diagnostic gold standard, they detect pathogens in only a minority of suspected cases. This study compared the accuracy of blood cultures with a rapid multiplex PCR test. Newborns at risk for neonatal sepsis were prospectively screened as recommended per national guidelines. Evaluations included laboratory parameters (CrP, IL6, differential blood count), blood culture, and a molecular multiplex PCR test (ROCHE LightCycler SeptiFast) identifying 20 common microbial agents. Blood samples were taken simultaneously from umbilical cord or venous sources on the first day of life. Of 229 infants included, 69% were born preterm. Blood culture and multiplex PCR sensitivity were 7.4% and 11.1% respectively. Specificity, negative and positive predictive values between methods showed no significant variance, though multiplex PCR had more false positives due to contamination. The limited sensitivity of blood cultures for early onset neonatal sepsis is concerning. Despite quicker results, multiplex PCR does not enhance diagnostic accuracy or antibiotic therapy guidance, thus it can not be recommended for this indication.

Abstract: Background: Neonatal sepsis continues to be one of the leading causes of mortality and morbidity, particularly in under development and underdeveloped countries. We aim to compare laboratory parameters between the early-onset sepsis (EOS) and non-EOS groups and to evaluate the association between TLR2- Arg753Gln, TLR4 -Asp299Gly, IL6-174G/C and IL10-1082G/A gene single nucleotide polymorphisms and EOS susceptibility in preterm newborns. Methods: Genotyping of the TLR2, TLR4, IL6 and IL10 polymorphisms was performed in 36 preterm neonates by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). Logistic regression analysis was used to test the associations between the studied gene polymorphisms and EOS susceptibility. Results: Statistically significant differences in gestational age and birth weight were observed between the two groups, preterm neonates with EOS having a lower mean of gestational age (weeks, 29.4 ± 2.8 versus 32.6 ± 1.1, p = 0.00002) and lower mean of birth weight (gr., 1342.1 ± 446.5 vs. 1984 ± 376.9) than preterm neonates without EOS. C-reactive protein (CRP) values measured at first day significantly increased in EOS group compared with non-EOS group (median, 95% CI: 0.80 [0.40, 1.15] versus 0.30 [0.02, 0.50]). Mean of neutrophils significantly decreased in the EOS preterm neonates (mean difference: 17.3%, 95% CI: [4.0%, 30.5%], p = 0.0126) and non-EOS group (mean difference: 20.8%, 95% CI: [1.8%, 39.9%, p = 0.0354) between the first day and 7th hospitalization day. The minor IL10-A1082 allele frequency was higher in the EOS group than in the nonEOS group (50% versus 25%) with a marginal statistical significance (p=0.0550). In the dominant model, the A/G + A/A variant genotype of IL10- 1082G/A polymorphism significantly increased the odds of EOS compared with GG genotype (OR= 5.25, p = 0.0322). Conclusions: The results of the current study suggests the IL10- 1082G/A gene polymorphism as significant risk factor for early onset sepsis development in preterm neonates.

Preterm delivery can be precipitated by infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. 90 infants had suspected prenatal infection and 63 were diagnosed with postnatal infection. Independent of gestational age at delivery, MCP-1 was significantly increased (P &lt; 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (P&lt;0.01) and CRP was increased (P&lt;0.05) in the presence of chorioamnionitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age. In those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants born exclusively for maternal indications.

Neonatal brain injury remains a significant issue with limited treatment options. The endogenous neurosteroids dehydroxyepiandrosterone (DHEA) and its sulfate ester (DHEAS) have demonstrated promising therapeutic potential in adult brain injury models due to their neuroprotective mechanisms. This study aimed to analyze the neuroprotective potential of DHEA and DHEAS with a particular interest in anti-oxidative properties in a mouse model of neonatal hypoxic-ischemic brain injury. Using the modified Rice-Vanucci model, brain injury was induced in 7-day-old mouse pups, followed by treatment with various concentrations of DHEA and DHEAS (0.1, 1, and 10 µg/g body weight) via intraperitoneal injection after a 2-hour recovery period. Mice were sacrificed after 24 hours for analysis of somatometry, brain injury, apoptosis, microglial activation, and oxidative stress markers (NOX2, 4-HNE, 8-OHdG), along with the anti-oxidant marker SOD1. No statistically significant effects of the treatments were observed at the tested doses and time points. Although this study did not conclusively demonstrate the anti-oxidative neuroprotective potential of DHEA or DHEAS, neither substance exhibited toxic or harmful effects. Several factors may have contributed to the lack of observable effects, underscoring the need for further refinement in future studies of DHEA(S) and other treatments of neonatal hypoxic-ischemic brain injury.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Nasal high-frequency oscillatory ventilation (nHFOV) has emerged as an effective initial and rescue noninvasive respiratory support mode for preterm infants with respiratory distress syndrome (RDS). Multiple noninvasive respiratory support modes are currently available in Romania, but little is known about nHFOV use in Romanian neonatal intensive care units (NICUs). We aimed to identify the usage extent and clinical application of nHFOV in Romania. A structured web-based questionnaire was designed to find the rate of nHFOV use and knowledge of this new method of noninvasive respiratory support in Romanian level III NICUs. The questionnaire was addressed to the leaders of all level III Romanian NICUs. Using multiple-choice, open-ended, and yes/no questions, we collected information on the NICU’s size, noninvasive respiratory support modes used, nHFOV use, indications, settings, nasal interfaces, secondary effects, and equipment used. Descriptive statistics and comparisons were performed using IBM SPSS Statistics 26.0. A total of 21/23 (91.3%) leaders from level III NICUs (median [IQR] number of beds of 10 [10-17.5]) responded to the survey. The most frequently used noninvasive ventilation modes were CPAP mode on mechanical ventilators (76.2%), followed by NIPPV (76.2%), heated, humidified high flow nasal cannula (HHHFNC) (61.9%), and nHFOV (11/21 units; 52.4%); 5/11 units reported frequent nHFOV use (in 2 or more newborns/month) in both term and preterm infants. The main indications reported for nHFOV use were CPAP failure (90.9%), hypercapnia (81.8%), and bronchopulmonary dysplasia (72.7%). 10/11 units reported setting a mean airway pressure (MAP) equal to the CPAP level plus 1-2 cmH₂O on rescue nHFOV after CPAP failure. Both dedicated equipment (45.5%) and hybrid ventilators (63.6%) were used for nHFOV delivery, with face/nasal masks and short binasal prongs being the most commonly used nasal interfaces (90.9% and 72.7%, respectively). Air leaks at the interface level (90.9%), thick secretions (81.8%), and airway obstruction (63.6%) were the most frequently mentioned adverse effects of nHFOV; none of the units mentioned pneumothorax as an adverse effect. Only 3 of the NICUs had a written protocol for nHFOV use. Initial, minimum, and maximum amplitude and initial and minimum MAP settings used were significantly higher with hybrid ventilators as compared to dedicated equipment (p<0.05). Most units not yet using nHFOV cited lack of equipment, experience, training, or insufficient information and evidence for the clinical use and outcome of nHFOV use in neonates as the main reasons for not implementing this noninvasive respiratory mode. Our survey showed that nHFOV is already used in more than half of the Romanian level III NICUs to support term and preterm infants with respiratory distress despite a lack of consensus regarding indications and settings during nHFOV. A need for training for nHFOV use was identified, and efforts are needed at the national level to develop courses and training sessions, including using simulation workshops, to offer more information on optimal nHFOV use in clinical practice.

During the last decades, a growing number of studies have shown that infections during pregnancy have an important impact on both pregnant women and their fetuses. Our goal was to identify newborns from pregnancies with SARS-CoV-2 infection and to investigate the extension of neonatal complications using cardiac, abdominal and cerebral ultrasonography, hearing testing and indirect ophthalmoscopy. By contrast, neonates whose mothers were vaccinated against COVID-19 during pregnancy and those from pathology-free pregnancies have been examined. A total of 458 newborns were included, over a period of 10 months, divided into 3 groups, COVID-19 group, vaccine group and control group. Although 6 cardiac malformations were found in the COVID-19 group, no correlation was made compared to the vaccine and control group (p=0.07). Grade 1 intraventricular hemorrhage and hypoxic ischemic encephalopathy were the most prevalent among neonates from mothers with SARS-CoV-2 infection (p=0.002 and p&lt;0.001, respectively). The kidney anomaly found to be most frequent in this group was grade 1 unilateral hydronephrosis (p&lt;0.001). COVID-19 disease during the gestational period had no effect on the auditory or visual function. Despite the fact that our observations are relevant, further studies investigating the effects of SARS-CoV-2 infection during pregnancy and the neonatal outcomes are necessary.

Perinatal brain injury is a major public health problem burdened with high morbidity, mortality and severe neurological sequelae. Despite advances in neonatal life-saving technologies, neonatal encephalopathy lacks specific and effective treatment. Therefore, mechanisms of central nervous system changes associated with perinatal brain injury have been a hot topic of neonatology research. In recent years, researchers have shifted more focus from neurons themselves to perineuronal cells and intercellular interactions. As a member of the nervous system network, astrocytes are one of the dominant glial cells that regulate ion homeostasis, blood flow, and antioxidant function in the brain. Their changes in molecular mechanisms (e.g., alterations in RNA regulatory networks) during brain injury storms deserve further attention. Non-coding RNAs participate in and promote reactive pathophysiologic changes in astrocytes. The review summarizes and discusses the role of non-coding RNAs in astrocytes in recent years in studies of neonatal brain injury. It focuses on the most studied disease-related ncRNAs: miRNAs, lncRNAs and circRNAs, and hopes to provide possible directions for pathophysiological studies and therapeutic approaches of neonatal brain injury.

An 18 month-old male was evaluated after presenting with disproportionate transaminitis in the setting of acute gastroenteritis. He had marked hepatomegaly on physical exam that was later confirmed with an abdominal ultrasound. Given this clinical picture, suspicion for a fatty acid oxidation disorder was raised. Further investigation revealed that his initial newborn screen was positive for carnitine palmitoyltransferase 1A (CPT1A) deficiency - a rare autosomal recessive disorder of long-chain fatty acid oxidation. Confirmatory biochemical testing in the newborn period showed carnitine levels to be unexpectedly low with a normal acylcarnitine profile. Thus, it was considered to be a false-positive newborn screen and metabolic follow up was not recommended. Repeat biochemical testing during this hospitalization revealed a normal acylcarnitine profile. The only abnormalities noted were a low proportion of acylcarnitine species from plasma, an elevated free-to-total carnitine ratio, and mild hypoketotic medium chain decarboxylic aciduria on urine organic acids. Gene sequencing of CPT1A revealed a novel homozygous splice site variant that confirmed his diagnosis. CPT1A deficiency has a population founder effect in the Inuit and other Arctic groups, but has not been previously reported in persons of Ashkenazi Jewish ancestry.

Introduction: Management of hypoxic-ischemic encephalopathy (HIE) has been the subject of international recommendations. However, some aspects remain within the realm of service practices and appear to vary greatly from one center to another. Objectives: To achieve a multidisciplinary consensus in France regarding management of HIE newborns that are not covered by international and national guidelines. Methods: This is a prospective, multicenter study using the Delphi method from April 21, 2021, to July 15, 2021. Perinatal professionals were contacted through professional societies. Participants received a questionnaire in three successive rounds. Each proposal was rated using a Likert scale from 1 (completely disagree) to 8 (completely agree). An item was considered consensual if at least 70% of responses were in agreement or disagreement. Results: 58 french neonatal professionals participated. A consensus was reached in the first round concerning the use of passive hypothermia in maternity ward, with 84% agreement and to define the target temperature between 35.0°C and 35.5°C at the third round. Regarding hypoglycemia in the delivery room, 79.2% agreed in the first round to correct blood glucose levels below a threshold of <2.2 mmol/l. Parenteral route was the preferred correction method for 91.4% of respondents, while enteral route via nasogastric tube did not reach consensus. Conclusion: This study highlights the variability in definitions and practices among professionals in the management of HIE. Consensus was found regarding certain care practices performed without formal guidelines. The work to harmonize definitions and practices for the management of HIE likely needs to continue.

This study aims to explore the associations between pediatric adverse events (PAEs) and hospital and patient characteristics within the inpatient hospital setting, focusing solely on the framework of pediatric quality indicators (PDIs) from the Agency for Healthcare Research and Quality (AHRQ). Specifically, the study focuses on NQI 03 Neonatal Blood Stream Infection (NBSI). The analysis utilizes discharge data from the Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Databases (KID) for the year 2019. Through this analysis, the study seeks to answer research questions regarding associations between hospital characteristics and patient characteristics with NQI 03. The methodology employs bivariate and multivariate logistic regression models to analyze patient-level encounters of NBSI. The results indicate that smaller, rural, and non-teaching hospitals exhibit significantly lower odds of NQI 03 compared to large hospitals. Various individual factors such as gender, age, race, service lines, payment sources, and major operating room procedures also demonstrate differing levels of significance in relation to NQI 03, warranting further investigation. This study provides contextual expansion on the findings and offers valuable insights into PAEs in the inpatient hospital setting, specifically focusing on NBSI within the PDIs framework. It highlights areas for developing evidence-based interventions and guidelines for clinicians and policymakers. Ultimately, the findings contribute to the growing understanding of factors influencing NBSI and emphasize the importance of targeted strategies for improving pediatric patient safety.

Existing research concerning the effects of the sitting birth position during the second stage of labour on maternal and neonatal outcomes remains controversial, and there is a lack of studies to explore its effect on the childbirth experience. The objective of this study is to explore whether the sitting birth position would influence maternal and neonatal outcomes, as well as the childbirth experience reported by Chinese women using the Childbirth Experience Questionnaire (CEQ). A total of 296 women (including primiparous women and multiparous women) were enrolled in our study, and they were divided into the sitting position cohort (n=106) or the lithotomy position cohort(n=116). The study found that primiparous women in the sitting position cohort had a shorter duration of the second stage of labour, higher spontaneous vaginal birth rates, lower episiotomy rates and better childbirth experience (p<0.01). There was no significant difference for perineal lacerations, 2h-postpartum haemorrhage (P>0.05) between the two cohorts of primiparous women. After adjusting for confounding factors through multiple linear and logistic regression analyses, the results remained consistent with those reported above. No neonate in each cohort had Apgar scores at 1min and 5 min postpartum less than 7 or the Cord artery pH less than 7.00, regardless of parity. In addition, among multiparous women, there was no significant difference in any maternal and neonatal outcomes and women’s CEQ scores (p>0.05) between two cohorts. Based on the findings, we recommend that women could take the sitting birth position into account when giving birth for a positive childbirth experience, especially for primiparous women. The study could also serve as a reference for healthcare providers in the management of childbirth positions and the development of high-quality maternal care.

The effects of hypothermia on neonatal encephalopathy may vary regionally, spatially, and cytopathologically in the gyrencephalic neocortex with manifestations potentially influenced by seizures that alter the severity and distribution of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia with continuous encephalographic (cEEG) monitoring for seizures to study injury in neocortex. Neonatal piglets were randomized to naïve, HI-normothermia (NT), overnight hypothermia (HT) initiated 2 hours after HI, sham-NT, or sham-HT treatments. Some piglets within sham and HI groups received cEEG monitoring during recovery. Survival was 2-7 days (piglets were unmedicated and those with poor recovery and unresolving seizures were euthanized early); there was no differences in survival among groups (p&gt;0.078). Neuropathology was assessed by hematoxylin and eosin staining and immunohistochemistry for RNA Binding FOX-1 Homolog 3 (Rbfox3/NeuN). Normal and ischemic-necrotic neurons were counted (layers II-VI collectively) in somatosensory, motor, and prefrontal cortices, identified by cytoarchitecture and connectomics, and in inferior parietal cortex by layer. Seizure burden was determined. HI-NT piglets had reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to naïve, sham-NT, and sham-HT piglets in anterior and posterior motor and somatosensory cortices. Frontal cortex was vulnerable in the prefrontal lateral bank after HI-NT with ischemic-necrosis. HI-HT piglets had higher normal/total neuron ratios and lower ischemic-necrotic/total neuron ratios than HI-NT piglets in anterior/posterior motor and somatosensory cortices. Total normal neuron density in layer III of inferior parietal cortex was reduced in HI-NT piglets compared to sham piglets and was protected by HT. Laminar analysis of Rbfox3 in somatosensory cortex revealed three types of neurons: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT. Cortical neuron Rbfox3-depletion was partly rescued by HT. Seizure burden was more severe in HI piglets compared to sham piglets, but HI-NT and HI-HT piglets were similar. We conclude that 1) the neonatal piglet neocortex has a suprasylvian spatial vulnerability to HI and seizures; 2) HT protects against neuropathology in functionally different regions of the neonatal gyrencephalic neocortex; 3) neurons in neonatal neocortex have a limited cytopathology repertoire seen by H&amp;E staining; 4) higher seizure burden correlates with more ischemic-necrotic neurons in somatosensory cortex; 5) seizure presence associates with damage spread to inferior parietal cortex; 6) seizure presence is insensitive to HT, and 7) Rbfox3 immunophenotyping identifies a novel neuronal RNA splicing protein nuclear-depletion pathology that appears reversible by HT. This work demonstrates that HT protection of neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores depleted neuronal RNA splicing factor.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its im-pact on neonatal outcomes and respiratory morbidity has not yet been extensively studied. In this context, it is crucial to understand the underlying mechanisms of neonatal complications. Moreover, no study has yet demonstrated the effectiveness of antenatal corticosteroid therapy (CT) for prevention of the respiratory distress syndrome (RDS) in newborns of mothers with PAS at the molecular level. In this regard, miRNA profiling was performed on 160 blood plasma sam-ples from preterm infants (gestational age 33–36 weeks) and their mothers diagnosed with or without PAS. The samples with PAS were categorized into groups: without antenatal RDS prophylaxis, and with CT admin-istered either 2–7 days, 7–14 days, or more than 14 days before delivery. These groups were compared to a control group without PAS in the absence of antenatal CT. Deep sequencing was conducted using the NEB-Next® Multiplex Small RNA Library Prep Set for Illumina® on the NextSeq 500/550 platform, followed by validation by quantitative real-time PCR. A significant increase in hsa-miR-199a-3p and hsa-miR-382-5p levels was observed in the blood plasma of newborns with PAS (placenta accreta and increta) compared to the control group. In maternal blood, hsa-miR-199a-3p levels were markedly higher than hsa-miR-382-5p. The timing of antenatal CT significantly influenced the levels of hsa-miR-199a-3p and hsa-miR-382-5p in neonatal plasma from mothers with placenta accreta or increta. A clear trend toward normalization was observed when CT was administered within 14 days before delivery, particularly in the seven days before delivery, but not beyond 14 days. Among newborns with PAS, higher levels of hsa-miR-382-5p were significantly associated with increased Neomod scale severity scores of 2, 4, and 5 compared to a score of 0. Additional-ly, a direct correlation was found between hsa-miR-382-5p level in neonatal plasma and hsa-miR-199a-3p level in the same sample (r = 0.49; p = 0.0001), oxygen requirements in the NICU (r = 0.41; p = 0.0016), duration of NICU stay (r = 0.31; p = 0.019), and the severity of the newborn’s condition based on the NEOMOD scale (r = 0.36; p = 0.0051). Logistic regression mod-els based on maternal plasma levels of hsa-miR-199a-3p and hsa-miR-382-5p predicted the need for cardiotonic therapy, invasive mechanical ventilation, or high-frequency oscillatory ventila-tion in newborns during the early neonatal period, with a sensitivity of 95-100%. It was con-cluded that elevated circulating levels of miRNAs, hsa-miR-199a-3p and hsa-miR-382-5p, in ma-ternal and fetal blood are crucial in the development of respiratory and cardiac complications in newborns from pregnancies affected by PAS. These miRNAs regulate surfactant synthesis in al-veolar cells, fetal organogenesis via IGF-1, the formation of proper lung tissue architecture, and vascular tone.

Background: Echovirus 11 (EV-11) is a notable enterovirus linked to severe infections in neonates, often resulting in significant morbidity and mortality. In April 2019, an EV-11 outbreak occurred in the sick neonate room at a teaching hospital in Taichung, Taiwan, posing a serious threat to the vulnerable infants in this setting. Objectives: This study aimed to identify the source and transmission dynamics of the EV-11 outbreak in the neonatal unit and evaluate the effectiveness of the infection control measures implemented to contain the outbreak. Methods: Patient records, epidemiological data, and laboratory findings were reviewed. For all cases, confirmatory tests were performed using virus isolated from cerebrospinal fluid. Rapid quarantine measures were employed. The hospital’s nosocomial infection surveillance system was used to track confirmed cases and exposed individuals to facilitate effective management and monitoring; Results: Five neonates were confirmed to have EV-11 during the outbreak. Surveillance of 10 contacts and 11 newly admitted cases yielded negative results. All infected infants eventually recovered. The cohort comprised three males and two females, with a birth weight range of 2472–4224 grams. Their gestational ages range of 34 3/7 weeks to 39 weeks; including two premature and three full-term infants. Symptoms began between 6 and 27 days of life, with fever being the consistent clinical manifestation. Strict infection control measures, including isolation of infected cases, suspension of rooming-in, and rigorous disinfection protocols, successfully halted viral spread. The outbreak was contained within 39 days, with no additional cases reported post-intervention; Conclusions: The prompt and effective response, including robust infection control protocols, was crucial for managing and containing the EV-11 outbreak in the neonatal unit. These cases underscore the significance of immediate action, stringent infection control measures, and ongoing monitoring for addressing enterovirus outbreaks in neonatal care settings.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight <1000g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomised to AF group and 23 to TF group. AF was based on BUN concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day).No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge nor during intervention. Protein intake was significantly higher in AF group (5.02 g/kg/day vs 4.48 g/kg/day, p= 0.001). No differences were found in lipids, carbohydrates and energy intake; neither in weight z score change between the different time points; nor in length and head circumference growth. Both AF and TF are comparable methods of fortification and provide appropriate growth rate in ELBW infants.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

Background: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well-documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia. Methods: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates diagnosed at Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia, between October 5, 2020, and November 5, 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. Results: The total sample size was 181. The average age of patients was 34 years (SD=6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25-1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38-2.19), LBW (aOR = 1.32, 95% CI: 1.06-1.66), and RDS (aOR = 1.57, 95% CI: 1.28-1.93) were significantly higher among neonates born to mothers with MDM. Types of DM were statistically significant with some neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). Conclusion: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. Early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population.

Background: Parents of preterm infants face major mental health challenges in the Neonatal Intensive Care Unit (NICU). Family-centered music therapy actively integrates and empowers parents in their infant’s care. With the aim to better understand and address parental needs separately from their babies’, a music therapy (MT) self-care group was implemented as part of clinical practice at the hospital Clínica de la Mujer in Bogotá, Colombia. Methods: The group is provided for both parents twice a week in the NICU. Music guided relaxations, breathing techniques, and self-expression are at the center of the MT group sessions. Parents complete a pre/post self-administered Numeric Rating Scale (NRS) including anxiety levels, stress levels, mood and motivation. Results: Parents highly value the MT self-care group at the NICU. On average there is a 37% improvement in anxiety levels, 28% in stress levels, and 12% in mood, restfulness and motivation. Being able to relax, to distract themselves from their worries and having time for themselves are amongst the most frequently mentioned benefits. Conclusions: Addressing parents’ needs separately form their babies’ treatment with culturally sensitive interventions aimed to improve parental mental health, is essential for continuing the development of family-centered music therapy interventions in the NICU.

This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a 2-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 hours of blood culture incubation (range 7.5-20 hours), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which of Streptococcus epidermidis in neonates with LOS and one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay.

It is documented that maternal diseases or treatments influence a newborn’s clinical status at birth; autoimmune diseases with circulating antibodies are often clinically expressed transiently in newborns due to the crossover of the specific IgG through the placenta during pregnancy. The offspring can inherit maternal genetic anomalies, but clinical expression usually becomes patent later in life. If prenatal medical history is not available or if signs or symptoms of a mother’s disease are revealed for the first time during pregnancy or postpartum, their effects on the newborn may be misattributed. In this article, we present three cases of pregnant women, without any known pathology before or during pregnancy, who gave birth to very sick preterm newborns that required admission to the Neonatal Intensive Care Unit (NICU). The neonates’ complications were considered initially as consequences of prematurity or infection, but later investigations revealed transient autoimmune disease in two of the cases (myasthenia gravis and hyperthyroidism) and a severe form of thrombophilia in the third case. In all cases, mothers were asymptomatic and unaware of their subclinical disease. Preemies’ diagnosis has contributed to the identification of their mothers’ pathology and adequate treatment was prescribed with favourable short- and long-term outcomes. In one of the cases (myasthenia gravis) both mother and child had associated infectious diseases in the perinatal period that complicated the clinical picture and created problems of diagnosis. This article intends to emphasize the paramount importance of prenatal care, for both mother and newborn. Repeated medical visits and investigations throughout the pregnancy are a good opportunity to detect subclinical diseases or predispositions. As newborns usually develop non-specific signs, one should have experience and pay attention to differentiate among etiologies. Our paper takes a reversed approach to the usual medical diagnosis pathway: from infant to mother instead of mother towards the infant, proving that inter-speciality collaboration can work bi-directionally.

Sepsis still remains one of the most difficult conditions to diagnose as it presents unspecific clinical signs and symptoms, which makes early detection crucial. Our study aimed to enhance the accuracy of sepsis diagnosis by integrating multimodal monitoring technologies with traditional diagnostic methods. The research involved 121 newborns, comprising 39 cases of late-onset sepsis, 35 cases of early-onset sepsis, and 47 control subjects. Biosignals including pulse oximetry (PO), near-infrared spectroscopy (NIRS), and skin temperature (ST) were continuously monitored and an algorithm was developed using Python for identifying early signs of sepsis. The model demonstrated the ability to detect sepsis 6 to 48 hours in advance with an accuracy rate of 87.67% ± 7.42%. Sensitivity and specificity were recorded at 76% and 90%, respectively, with NIRS and ST having the most significant impact on predictive accuracy. Despite the promising results, limitations such as sample size, data variability, and potential biases were noted. The findings highlight the critical role of non-invasive biosensing methods in conjunction with traditional biomarkers and cultures, offering a robust framework for early sepsis detection and improved neonatal care. Further studies are recommended to validate these results across diverse clinical settings.

Opioid analgesics are effective pain therapeutics but cause various adverse effects and addiction. For safer pain therapy, biased opioid agonists selectively target distinct m opioid receptor (MOR) conformations, while the potential of biased opioid antagonists has been neglected. Agonists convert a dormant receptor form (MOR-m) to a ligand-free active form (MOR-m*), which mediates MOR signaling. Moreover, MOR-m converts spontaneously to MOR-m* (basal signaling). Persistent upregulation of MOR-m* has been invoked as a hallmark of opioid dependence. Contrasting interactions with both MOR-m and MOR-m* can account for distinct pharmacological characteristics of inverse agonists (naltrexone), neutral antagonists (6b-naltrexol), and mixed opioid agonist-antagonists (buprenorphine). Upon binding to MOR-m*, naltrexone but not 6b-naltrexol suppresses MOR-m*signaling. Naltrexone blocks opioid analgesia non-competitively at MOR-m*with high potency, whereas 6BN must compete with agonists at MOR-m, accounting for ~100-fold lower in vivo potency. Buprenorphine’s bell-shaped dose-response curve may also result from opposing effects on MOR-m and MOR-m*. In contrast, we find that 6b-naltrexol potently prevents dependence, below doses affecting analgesia or causing withdrawal, possibly binding to MOR conformations relevant to opioid dependence. We propose that 6b-naltrexol is a biased opioid antagonist modulating opioid dependence at low doses, opening novel avenues for opioid pain therapy and use management.

Very little is known about laboratory confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design antibiotic interventions to reduce LCBIs in resource-limited settings.

Perinatal mortality is a major issue in laboratory mouse breeding. We compared a counting method using daily checks (DAILY_CHECK) with a method combining daily checks with detailed video analyses to detect cannibalisms (VIDEO_TRACK) for estimating the number of C57BL/6 pups born, died and weaned in 193 litters from trios with (TRIO-OVERLAP) or without (TRIO-NO_OVERLAP) the presence of another litter. Linear mixed models were used at litter level. To understand if cannibalism was associated with active killing (infanticide), we analysed VIDEO_TRACK recordings of 109 litters from TRIO-OVERLAP, TRIO-NO_OVERLAP or SOLO (single dams). We used Kaplan-Meier method and logistic regression at pup level. For DAILY_CHECK, the mean litter size was 35% smaller than for VIDEO_TRACK (P&lt;0.0001) and the number of dead pups was twice lower (P&lt;0.0001). The risk of pup loss was higher for TRIO-OVERLAP than TRIO-NO_OVERLAP (P&lt;0.0001). A high number of pup losses occurred between birth and the first cage checking. Analyses of VIDEO_TRACK data indicated that pups were clearly dead at the start of most of the cannibalism events and infanticide was rare. As most pups die and disappear before the first cage check, many breeding facilities are likely to be unaware of their real rates of mouse pup mortality.

Background: Globally, infections are the third leading cause of neonatal mortality. Predominant risk factors for facility-born newborns are poor hygiene practices that span both the facility and home environments. Current improvement interventions focus on only one environment and tar-get limited caregivers, primarily birth attendants and mothers. To inform the design of a hand hygiene behaviour change intervention in rural Cambodia, a formative mixed-methods research study was conducted to investigate the context specific behaviours and determinants of hand-washing among healthcare workers, maternal and non-maternal caregivers along the early new-born care continuum. Methods: Direct observations of hygiene practices of all individuals providing care to 46 newborns across eight facilities and associated communities were completed and hand hygiene compliance assessed in analysis. Semi structured interactive interviews were subsequently conducted with 35 midwives and household members to explore the corresponding cognitive, emotional, and environmental factors influencing the observed key hand hygiene behaviours. Results: Hand hygiene opportunities during newborn care were frequent in both set-tings (n = 1319) and predominantly performed by mothers, fathers and non-parental caregivers. Compliance to hand hygiene protocol across all caregivers, including midwives, was inadequate (0%). Practices were influenced by the lack of accessible physical infrastructure, time, increased workload, low infection risk perception, nurture-related motives, norms and inadequate knowledge. Conclusion: Our findings indicate that an effective intervention in this context should be multi-modal to address the different key behaviour determinants and target a wide range of caregivers.

Introduction: There are no clear guidelines to support adequate nutrition and growth for our neonates. We have used the difference in weight Z-score medians between birth and discharge (∆ Z-score) to assess the nutritional outcomes in EpicLatino. The ∆ Z-score is often negative, accounting for the desirable fluid contraction at birth that sends the preterm baby usually between 0.5-1 weight Z-score point down the curve. From then on, most researchers accepted a healthy and safe growth parallel to the intrauterine rate. No consensus on the optimal timing for assessment or the ideal growth monitoring tool has been achieved, and an ongoing debate persists on the appropriate terminology to express poor postnatal growth.Methods: We analyzed data from the past 8 years (2015-2022) in surviving home to at least 34 weeks corrected age infants with ≤ 32 weeks gestational age at birth (GA). We conducted a series of statistical comparisons with variables that have been mentioned as potential causes of poor nutrition in the literature. We used the weight ∆ Z-score from birth to discharge as a surrogate for nutrition. We obtained the weight median and interquartile range (IQR) from all the EpicLatino units. We also calculated the correlation between weight ∆ Z-score and gestational age and head circumference (HC) at discharge.Results: There were 480 cases that meet the established criteria. Gestational age at birth, necrotizing enterocolitis (NEC), unit of origin, rupture of membranes (ROM) > 24 hours, temperature at admission, and intraventricular hemorrhage (IVH) were significantly different. There was a negative correlation between ∆ Z-score and corrected gestational age at discharge. Head circumference at discharge also correlated with weight ∆ Z-score.Discussion: There is an important variability in the different units of origin. Also, when looking for risk factors, we confirmed that the characteristics of the study population are determinant to extrauterine growth restriction (EUGR) at discharge. As is known, these associations do not establish causality, some of these variables may identify the challenge of nourishing a sick or very small preterm infant, but the unit of origin variable identifies nutrition policies and practices that can be modified through a quality improvement program.

Our objective was to evaluate whether pregnancy is prolonged by use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in preterm birth rate. Rather than considering a dichotomous outcome (preterm vs term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, P &lt;0.01). Newborns of screened subjects had significantly shorter NICU stay but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We concluded that screening with the PreTRM test followed by interventions for screen-positive pregnancies can prolong pregnancy and reduce NICU-LOS.

Vitamin D plays an essential role in embryogenesis and the course of intra- and postnatal periods and is crucially involved in the functioning of the mother-placenta-fetus system. Low quantity of Vitamin D during pregnancy can lead to the elevated risk for preeclampsia occurence. Despite the numerous studies on the association of Vitamin D deficiency and preeclampsia development, the current research on this theme is contradictory. In this review we summarize and analyze study data on the effects of vitamin D deficiency and supplementation on pregnancy, labor, fetal and neonatal outcomes.

The monitoring of sick newborns is a challenging task that health care providers in Neonatal Intensive Care Units (NICU) must contend with each day. Conventionally, newborns are monitored via probes that are affixed to their skin and attached to processing monitors (Fig.1). However, an alternative exists in contactless imaging to record such physiological signals (Physio-Markers), surface changes and internal structures which can be used independently of, or in conjunction with conventional monitors. Advantages of contactless monitoring methods include: i) quick data generation; ii) lack of contact with skin, which reduces skin breakdown and decreases risk of infection; and iii) minimizing the number of probes and monitors affixed to the skin, which allows greater body surface-area for other care. This paper is an attempt to build a foundation for and to provide a vision of the potential neonatal clinical applications of technologies that use non-contact modalities such as Visible Light Imaging (VLI), Near InfraRed Spectrum (NIRS), and Thermal Imaging (TI) using InfraRed Spectrum (IRS).

Aim: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from 6 hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. Secondary outcomes were composite adverse outcomes including pregnancy complications, delivery complications, and neonatal complications. Cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1,543 pregnant individuals in the standard screening group and 2,197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs 6.9%, respectively; p<0.0001). The primary outcome (large for gestational age rate) was similar between groups: 200/1543 (13.0%) vs 303/2197 (13.8%). The adjusted OR for this outcome was 1.74 (95% CI: 0.74-4.10). An adjusted analysis showed no differences between groups in composite adverse outcomes for pregnancy complications (OR: 1.11; 95% CI: 0.91-1.36), delivery complications (OR: 0.95; 95% CI: 0.75-1.19), and neonatal complications (OR: 1.28; 95% CI: 0.94-1.75). Among individuals diagnosed with GDM, the large for gestational age rate was similar between groups: 13/166 (7.8 %) vs 15/151 (9.9 %). The OR adjusted for this outcome was 1.24 (95% CI: 0.51-3.09). An adjusted analysis showed no differences in composite adverse outcomes for pregnancy complications (OR: 1.57; 95% CI: 0.84-2.98), delivery complications (OR: 1.21; 95% CI: 0.63-2.35), and neonatal complications (OR: 1.35; 95% CI: 0.61-3.04). The mean cost (which included expenses for consumables, equipment and personnel) of the alternative screening method was 46.0 euros (22.3 SD), as compared to 85.6 euros (67.5 SD) for the standard screening method. Conclusions: In this Spanish population during the COVID-19 pandemic, GDM prevalence was lower in the alternative screening group than in the standard screening group. After adjusting for GDM risk factors, outcomes related to obstetrics, delivery, and neonatal complications were comparable between both groups. Finally, the alternative screening method was cheaper than the standard screening method.

The efficacy of an intranasal (IN) bovine respiratory syncytial virus (BRSV) administered in the face of passive immunity was assessed. Pooled colostrum was administered by intubation to fifty (50) beef-dairy crossbred calves the day they were born. The calves were transported to a research facility and were blocked by age and sex and randomly assigned into two groups, a sham-vaccinated intranasally with a placebo (sterile water) or vaccinated with a tri-valent modified live viral (MLV) vaccine. The calves were 92 days old when vaccinated (day 0). The calves were challenged by aerosolized BRSV on day 80 and day 81 as a respiratory challenge. The study was terminated on day 88. Lung lesion scores (LLS) were significantly lower for calves vaccinated with tri-valent MLV vaccine than those for calves that were sham-vaccinated. Serum neutralization (SN) antibody against BRSV in calves vaccinated with the tri-valent MLV vaccine demonstrated an anamnestic response on day 88. After challenge, the calves sham-vaccinated with the placebo lost weight while those vaccinated with the tri-valent MLV vaccine gained weight. In this study colostrum-derived antibodies did not interfere with the immune response or protection provided by one dose of the tri-valent MLV vaccine.

Introduction: Since its discovery in late 2019, the novel coronavirus (SARSCOVID-2) that causes COVID-19 has spread fast, prompting the World Health Organization (WHO) to designate the disease a worldwide pandemic on March 11, 2020.The epidemic has profoundly altered the preexisting global sexual and reproductive health landscape .The virus’s load has put ordinary services in jeopardy and harmed other health priorities. This encompasses both the provision and the supply of contraceptives, sexual health, new born and maternal health services. This Scoping review therefore mapped the availability evidence on the impact and effects of the COVID-19 disease outbreak on sexual and reproductive health. Methods: The methodological framework by Arksey and O’Malley guided this scoping review. A literature search was conducted from the following databases: Embase, PubMed, CINAHL, Scopus, WOS, and AJOL. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) checklist were used to document the review process. The Strobe critical review checklist was used to determine the quality of the included studies. Results:19 studies were reviewed, out of which 4 were cross sectional studies, 1 was an observational study, 1 was a descriptive analytical study and the rest were qualitative studies .Majority of the studies showed evidence on the impact of COVID-19 and family planning service, maternal and child services, and three studies reported on COVID-19 and sexual behaviour. Five of the nineteen included studies reported on the impact of COVID-19 and family planning service. Conclusion: This scoping review has granted the assessment of the impact of novel SARS-CoV-2 on Sexual and reproductive health services with regards to sexual behaviour, family planning and maternal, neonatal and child health. From the 18 articles identified and reviewed, the overall responses stipulated a significant reduction in client’s utilization of services due to challenges experiences in service implementation such as stock outs. In addition, low demand for reproductive health services by clients due to restrictions imposed on the movements of people to curb the spread of the virus. It is therefore important that Governments and relevant stakeholders in Maternal and Sexual Reproductive Health prioritize development of policies and practices that protect women from the impacts of the pandemic. Furthermore, regular audits to detect trends in MSRH are necessary to inform on going mitigation efforts.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C&gt;T, not yet reported, and c.838C&gt;T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.