CSF1 is expressed by the intestinal epithelial cells to regulate Mφ macrophages and maintain epithelial homeostasis and is downregulated in neonates with necrotizing enterocolitis.

BACKGROUND: Colony stimulating factor 1 (CSF1) is generally expressed by immune cells in response to pro-inflammatory stimuli. The CSF1 receptor (CSFR) is activated by CSF1, and plays a key role in macrophage homeostasis. Furthermore, the CSF1R+ macrophages maintain homeostasis in the intestinal epithelium. The aim of this study was to explore the functions of CSF1-expressing and CSF1R+ macrophages in necrotizing enterocolitis (NEC), which commonly affects the ileum of neonates. METHODS: In-situ CSF1 expression in the intestines of neonates with NEC or intestinal atresia (n = 4 each) was detected by immunofluorescence staining. The CSF1 levels in the intestinal crypt-derived organoid cultures were measured by ELISA. Peripheral blood monocyte-derived Mφ macrophages were co-cultured with the organoids and stimulated with lipopolysaccharide (LPS) to mimic the inflamed state of the ileum in NEC patients. RESULTS: CSF1 was expressed in the intestinal epithelial cells of the fetal and neonatal samples, but suppressed in the NEC samples. Furthermore, CSF1 expression was downregulated in the intestinal crypt-derived organoids by LPS. CSF1R+ macrophages were detected near the intestinal crypts in the non-inflamed intestines but were absent in tissues obtained from pediatric NEC patients. Peripheral blood monocyte-derived macrophages promoted intestinal organoid proliferation in vitro following CSF1 stimulation. Finally, low concentrations of LPS slightly enhanced the proliferation of organoids co-cultured with the macrophages, whereas higher doses had a significant inhibitory effect. CONCLUSIONS: Intestinal epithelial cells express CSF1 to regulate the resident macrophages, maintain epithelial homeostasis, and resist infection. The abundant CSF1R+ macrophages in the fetal intestine may overexpress TNF-α upon activation of the TLR4/NF-κB pathway, resulting in epithelial damage and NEC induction.

Using cerebral regional oxygen saturation and amplitude-integrated electroencephalography in neonates on extracorporeal membrane oxygenation: preliminary experience from a single center.

OBJECTIVE: This study aims to evaluate the application value in neurological outcome of cerebral regional oxygen saturation (CrSO2) and amplitude-integrated electroencephalography (aEEG) monitoring during neonatal extracorporeal membrane oxygenation (ECMO) courses. METHODS: We retrospectively analyzed 18 neonates receiving veno-arterial ECMO (V-A ECMO) support at our hospital from July 2021 to December 2022. Continuous monitoring of CrSO2 and brain electrical activity was conducted using near-infrared spectroscopy (NIRS) and aEEG throughout the ECMO treatment. We collected and analyzed related clinical data. RESULTS: Among the 11 survivors, 5 were categorized as the normal group (N group) and 6 as the abnormal group (AN group) based on post-ECMO brain MRI outcomes. The N group exhibited shorter time percentage of significant CrSO2 reduction (> 25% from baseline or absolute value < 40%), better fractional tissue oxygen extraction (FTOE) rates, and more stable mean percentage changes in CrSO2 compared to the AN group. Neonates in the N group predominantly showed mildly abnormal aEEG readings, with one patient displaying disrupted sleep-wake cycles. This particular patient also had more significant CrSO2 reduction and poorer FTOE compared to others in the N group. Additionally, the Test of Infant Motor Performance (TIMP) scores indicated hypoevolutism in this patient before discharge, while others in the N group had normal TIMP scores. In the AN group, 4 exhibited moderate and 2 severe aEEG abnormalities; 5 had hypoevolutism TIMP scores, and 1 with moderate aEEG abnormalities maintained a normal TIMP score, exhibiting lesser CrSO2 reduction and improved FTOE. CONCLUSION: CrSO2 and aEEG monitoring show potential as routine assessments for neurological outcomes during neonatal ECMO. In our cohort, a tendency was observed where neonates with greater reductions in CrSO2 and more severe aEEG abnormalities experienced poorer neurological outcomes.

Fetal malnutrition among neonates in African countries: a CAN score systematic review and meta-analysis.

BACKGROUND: To reduce neonatal mortality, it is necessary to identify neonates with fetal malnutrition at birth using the clinical assessment score (CAN score). Furthermore, comprehensive summary data that shows burden of fetal malnutrition in Africa is scarce. As a result, this systematic review and meta-analysis aimed to assess fetal malnutrition among newborns in Africa. METHOD: The PRISMA guidelines were used for this study. Articles were obtained from databases and websites. The outcome of the study was fetal malnutrition, as determined using the CAN score. The meta-analysis of the primary and secondary outcomes was performed using Stata version 18 statistical software. The pooled prevalence with a 95% CI was estimated using the random effect method with the Der Simonian Liard model. RESULTS: This meta-analysis and systematic review included 5356 newborns from 13 studies. The pooled prevalence of fetal malnutrition (FM) among newborns diagnosed using the CAN score in Africa was 19% [95% CI: 17, 22]. Based on subgroup analysis by publication year, the lowest prevalence of fetal malnutrition 17% (95% CI: 9-27) was observed in the studies published in the years 2020-2023. Maternal and fetal factors were significantly associated with fetal malnutrition. CONCLUSION: Nearly one-fifth of neonates delivered in Africa were found to have fetal malnutrition based on the clinical evaluation of nutritional status. It has also been established that maternal malnutrition, a lack of proper treatment during pregnancy, maternal malnutrition, and newborn morbidities were associated with fetal malnutrition. To prevent fetal malnutrition, integrated efforts should be made for early maternal infection screening. Furthermore, maternal nutritional therapy should be explored for malnourished pregnant women.

Maternal dietary practices during pregnancy and obesity of neonates: a machine learning approach towards hierarchical and nested relationships in a Tibet Plateau cohort study.

Studies on obesity and risk factors from a life-course perspective among residents in the Tibet Plateau with recent economic growth and increasing obesity are important and urgently needed. The birth cohort in this area provides a unique opportunity to examine the association between maternal dietary practice and neonatal obesity. The study aims to detect the prevalence of obesity among neonates, associated with maternal diet and other factors, supporting life-course strategies for obesity control. A cohort of pregnant women was enrolled in Tibet Plateau and followed till childbirth. Dietary practice during pregnancy was assessed using the Chinese FFQ - Tibet Plateau version, food items and other variables were associated with the risk for obesity of neonates followed by logistic regression, classification and regression trees (CART) and random forest. Of the total 1226 mother-neonate pairs, 40·5 % were Tibetan and 5·4 % of neonates with obesity. Consuming fruits as a protective factor for obesity of neonates with OR (95 % CI) = 0·61 (0·43, 0·87) from logistic regression; as well as OR = 0·20 (0·12, 0·35) for consuming fruits (≥ weekly) from CART. Removing fruit consumption to avoid overshadowing effects of other factors, the following were influential from CART: maternal education (more than middle school, OR = 0·22 (0·13, 0·37)) and consumption of Tibetan food (daily, OR = 3·44 (2·08, 5·69). Obesity among neonates is prevalent in the study population. Promoting healthy diets during pregnancy and strengthening maternal education should be part of the life-course strategies for obesity control.

Usage of Antifungal Agents in Pediatric Patients Versus Adults: Knowledge and Gaps.

Invasive fungal infections (IFIs) present significant challenges in managing hospitalized and immunocompromised pediatric patients, contributing to high morbidity and mortality. Despite advancements in diagnostics and treatment, outcomes remain suboptimal due to unique clinical epidemiology, lack of pediatric-specific trials, and varied pharmacokinetics. The emergence of new antifungal classes and agents has expanded our options for preventing and treating IFIs in children, enhancing the safety and effectiveness of antifungal therapy. The oral formulations of ibrexafungerp, fosmanogepix and olorofim along with the extended dosing intervals of rezafungin show promising features for effective antifungal treatment in pediatrics. Despite the promising potential of novel antifungal drugs, their performance in heavily immunosuppressed patients remains unstudied. Until then, dedicated antifungal stewardship programs for high-risk patients are essential to optimize therapeutic outcomes, improve patient care, and limit the emergence of resistance.

Prevention of Recurrent Spontaneous Preterm Delivery Using Probiotics (Clostridium butyricum, Enterococcus faecium, and Bacillus subtilis; PPP Trial): Protocol for a Prospective, Single-Arm, Nonblinded, Multicenter Trial.

BACKGROUND: The rate of recurrent spontaneous preterm delivery (sPTD) ranges between 27% and 34% and is 22.3% in Japan. Although it currently remains unclear whether probiotics prevent sPTD, retrospective studies recently reported a reduction in the rate of recurrent sPTD with the administration of probiotics including Clostridium spp., which induce regulatory T cells that play an important role in maintaining pregnancy. OBJECTIVE: The objective of this trial is to evaluate the preventative effects of available oral probiotics, including Clostridium butyricum, on recurrent sPTD. METHODS: This is a prospective, single-arm, nonblinded, multicenter trial in Japan. The sample size required for this trial is 345 pregnant women with a history of sPTD, considering a clinically significant reduction in the relative risk of 30% (risk ratio=0.7). The primary endpoint is the rate of recurrent sPTD at <37 weeks of gestation. The secondary endpoints are the rate of sPTD at <34 weeks of gestation, the rate of recurrent sPTD at <28 weeks of gestation, the ratio of intestinal Clostridium spp. (detected by next-generation sequencing), and bacterial vaginosis (using the Nugent score). RESULTS: The trial procedures were approved by the Clinical Research Review Board of Toyama University Hospital (SCR2020008) on March 31, 2021. The trial was registered on the Japan Registry of Clinical Trial website on April 28, 2021. Recruitment began on May 1, 2021, and the trial is estimated to finish on March 31, 2025. CONCLUSIONS: The findings will clarify the rate of recurrent sPTD following probiotic administration including Clostridium butyricum. Outcomes from this trial will inform clinical practice and guide future randomized controlled trials. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs041210014; https://jrct.niph.go.jp/latest-detail/jRCTs041210014. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59928.

Correlation of anterior cerebral artery resistive index with early comorbidities in preterm neonates.

Introduction: This study was undertaken to find the clinical correlation of resistive index (RI) in the anterior cerebral artery (ACA) of preterm neonates admitted to the Neonatal Intensive care unit (NICU) with comorbidities such as perinatal asphyxia, neonatal sepsis, and necrotizing enterocolitis (NEC). Methods: An observational analytical study was conducted, including preterm neonates (<35 weeks) admitted to the NICU. Ultrasound cranium scans were performed on days 1-3 and 7 of life as per the study protocol. Baseline and clinical data of asphyxia, sepsis, and NEC were obtained. Images were acquired using a 4-8-MHz probe on a Sonosite M-turbo machine (Bothell, WA, USA). All statistical calculations were done using SPSS version 21.0 (SPSS Inc., Chicago, IL, USA) with the application of the Kolmogorov-Smirnov test and the Mann-Whitney test. Results: During the study period, a total of 739 neonates were admitted. Of these, 73 neonates constituted the study group. Among the 73 patients, 33 were preterm neonates without comorbidities and 40 neonates had comorbidities such as perinatal asphyxia, sepsis, and NEC stage 2 and 3 (necrotizing enterocolitis). In the present study, the mean RI on day 3 of life was 0.76 ± 0.04 in neonates without comorbidities and 0.77 ± 0.04 in neonates with comorbidities, with a p-value of 0.247. On the 7th day of life, the mean RI was 0.82 ± 0.03 in both groups, with a p-value of 0.42. Conclusion: We could not find any significant clinical correlation of RI in the ACA of preterm neonates <35 weeks of gestation with comorbidities.

Comparative Evaluation of Interpretation Methods in Surface-Based Age Prediction for Neonates.

Significant changes in brain morphology occur during the third trimester of gestation. The capability of deep learning in leveraging these morphological features has enhanced the accuracy of brain age predictions for this critical period. Yet, the opaque nature of deep learning techniques, often described as "black box" approaches, limits their interpretability, posing challenges in clinical applications. Traditional interpretable methods developed for computer vision and natural language processing may not directly translate to the distinct demands of neuroimaging. In response, our research evaluates the effectiveness and adaptability of two interpretative methods-regional age prediction and the perturbation-based saliency map approach-for predicting the brain age of neonates. Analyzing 664 T1 MRI scans with the NEOCIVET pipeline to extract brain surface and cortical features, we assess how these methods illuminate key brain regions for age prediction, focusing on technical analysis with clinical insight. Through a comparative analysis of the saliency index (SI) with relative brain age (RBA) and the examination of structural covariance networks, we uncover the saliency index's enhanced ability to pinpoint regions vital for accurate indication of clinical factors. Our results highlight the advantages of perturbation techniques in addressing the complexities of medical data, steering clinical interventions for premature neonates towards more personalized and interpretable approaches. This study not only reveals the promise of these methods in complex medical scenarios but also offers a blueprint for implementing more interpretable and clinically relevant deep learning models in healthcare settings.

First whole genome sequencing and analysis of human parechovirus type 3 causing a healthcare-associated outbreak among neonates in Hungary.

PURPOSE: In November 2023, the National Reference Laboratory for Enteroviruses (Budapest, Hungary) received stool, pharyngeal swab and cerebrospinal fluid samples from five newborns suspected of having human parechovirus (PEV-A) infection. The neonates were born in the same hospital and presented with fever and sepsis-like symptoms at 8-9 days of age, and three of them showed symptoms consistent with central nervous system involvement. PEV-A positivity was confirmed by quantitative reverse transcription polymerase chain reaction. METHODS: To determine the PEV-A genotype responsible for the infections, fecal samples of four neonates were subjected to metagenomic sequencing. For further analyses, amplicon-based whole genome sequencing was performed directly from the clinical samples. RESULTS: On the basis of whole genome analysis, sequences were allocated to PEV-A genotype 3 (PEV-A3) and consensus sequences were identical. Two ambiguities were identified in the viral protein 1 (VP1) region of all sequences at a frequency of 17.7-53.7%, indicating the simultaneous presence of at least two quasispecies in the clinical samples. The phylogenetic analysis and similarity plotting showed that all sequences clustered without any topological inconsistencies between the P1 capsid and P2, P3 non-capsid regions, suggesting that recombination events during evolution were unlikely. CONCLUSION: Our findings suggest that the apparent cluster of cases were microbiologically related, and the results may also inform future investigations on the evolution and pathogenicity of PEV-A3 infections.

Central Hypercapnia in a Neonate With Parechovirus Infection.

Human parechovirus infections in newborns often affect the central nervous system. It is common in children after infancy for it to be a cause of the common cold or be asymptomatic, but an infection in infancy often causes a central nervous system infection. Herein, we present the case of a nine-day-old infant who developed hypercapnia without any involvement of respiratory lesions. She showed no hypoxia or circulatory abnormalities. A high-flow nasal cannula relieved hypercapnia and consequent respiratory acidosis, suggesting that the hypercapnia was due to central ventilation failure with central nervous system infection despite no abnormalities on brain magnetic resonance imaging. Accurate diagnosis and intervention of ventilatory failure, which is a central nervous system dysfunction, is important in hypercapnia associated with parechovirus infection.

Key Influences on Oral Feeding Achievement in Preterm Infants: Insights From a Tertiary Hospital in Indonesia.

Objective: Effective oral feeding is one of the critical milestones that must be achieved by preterm infants. While gestational age and birth weight have been recognized as influential factors, recent studies have found additional variables impacting the achievement of full oral feeding (FOF). This study is aimed at describing factors associated with the attainment of FOF in preterm infants. Methods: This retrospective cohort study examines preterm infants born between 28 and 34 weeks' gestation admitted to Dr. Cipto Mangunkusumo General Hospital in Jakarta between July and December 2016. Comparative analysis utilized the Kruskal-Wallis test, while Cox's regression was employed for multivariate analysis to assess factors influencing the achievement of FOF. Results: This study included 87 preterm infants meeting the inclusion criteria. The median gestational age was 33 weeks (IQR: 3). The most common birth weight range was 1500-1999 g (51.7%). Median durations from birth to the first feed, full enteral feed, and FOF were observed to be 1 day (IQR: 1), 6 days (IQR: 10), and 14 days (IQR: 24), respectively. Notably, the duration of oxygen therapy, episodes of sepsis, and frequency of blood transfusions showed significant associations with the time taken to achieve FOF. Conclusion: This study found significant associations between the time to achieve FOF and factors such as oxygen therapy duration, sepsis episodes, and frequency of blood transfusion. These findings highlight the importance of considering these factors in managing preterm infants. However, a further prospective study is warranted to identify additional factors that influence feeding milestones in preterm infants.

Perceived Acceptability of Technology Modalities for the Provision of Universal Child and Family Health Nursing Support in the First 6-8 Months After Birth: Cross-Sectional Study.

BACKGROUND: Child and Family Health Nursing (CFHN) services provide universal care to families during the first 2000 days (conception: 5 years) to support optimal health and developmental outcomes of children in New South Wales, Australia. The use of technology represents a promising means to encourage family engagement with CFHN services and enable universal access to evidenced-based age and stage information. Currently, there is little evidence exploring the acceptability of various models of technology-based support provided during the first 2000 days, as well as the maternal characteristics that may influence this. OBJECTIVE: This study aims to describe (1) the acceptability of technology-based models of CFHN support to families in the first 6 months, and (2) the association between the acceptability of technology-based support and maternal characteristics. METHODS: A cross-sectional survey was undertaken between September and November 2021 with women who were 6-8 months post partum within the Hunter New England Local Health District of New South Wales, Australia. Survey questions collected information on maternal demographics and pregnancy characteristics, perceived stress, access to CFHN services, as well as preferences and acceptability of technology-based support. Descriptive statistics were used to describe the characteristics of the sample, the proportion of women accessing CFHN services, maternal acceptability of technology-based support from CFHN services, and the appropriateness of timing of support. Multivariable logistic regression models were conducted to assess the association between maternal characteristics and the acceptability of technology-based CFHN support. RESULTS: A total of 365 women participated in the study, most were 25 to 34 years old (n=242, 68%), had completed tertiary level education or higher (n=250, 71%), and were employed or on maternity leave (n=280, 78%). Almost all (n=305, 89%) women reported accessing CFHN services in the first 6 months following their child's birth. The majority of women (n=282-315, 82%-92%) "strongly agreed or agreed" that receiving information from CFHN via technology would be acceptable, and most (n=308) women "strongly agreed or agreed" with being provided information on a variety of relevant health topics. Acceptability of receiving information via websites was significantly associated with maternal employment status (P=.01). The acceptability of receiving support via telephone and email was significantly associated with maternal education level (adjusted odds ratio 2.64, 95% CI 1.07-6.51; P=.03 and adjusted odds ratio 2.90, 95% CI 1.20-7.00; P=.02, respectively). Maternal age was also associated with the acceptability of email support (P=.04). CONCLUSIONS: Technology-based CFHN support is generally acceptable to mothers. Maternal characteristics, including employment status, education level, and age, were found to modify the acceptability of specific technology modalities. The findings of this research should be considered when designing technology-based solutions to providing universal age and stage child health and developmental support for families during the first 2000 days.

Characterization of Amniotic Fluid Ureaplasma Species from Pregnancies Complicated by Preterm Prelabor Rupture of Membranes.

The main aim of this study was to determine expanded sequence types (eSTs) of Ureaplasma species (U. spp.). DNA isolated from the amniotic fluid of pregnancies complicated by preterm prelabor rupture of membranes (PPROM) using an expanded multilocus sequence typing scheme. Additionally, the study sought to examine whether phylogenetic subgroups of U. spp. DNA differ with respect to maternal demographic and clinical parameters and selected aspects of short-term neonatal morbidity. This retrospective cohort study was focused on singleton pregnancies complicated by PPROM occurring between the gestational ages of 24+0 and 36+6 weeks, where amniocentesis was conducted to assess the intra-amniotic environment and the presence of U. spp. DNA in the amniotic fluid samples was confirmed. The stored aliquots of U. spp. DNA were used to assess differences in nucleotide sequences in six U. spp. genes (ftsH, rpL22, valS, thrS,ureG, and mba-np1) using the eMLST scheme. The expanded multilocus sequence typing scheme was performed in 73 samples of U. spp. DNA isolated from pregnancies complicated by PPROM. In total, 33 different U. spp. DNA eSTs were revealed, 21 (#20, 233-244, 248-251, 253, 255, 259, and 262) of which were novel. The most frequently identified eST was #41, identified in 18% (13/73) of the aliquots. Based on their genetic relationships, the U. spp. DNA was divided into two clusters and four subgroups [cluster I (U. parvum): A, 43% (n = 31); B, 15% (n = 11); and C, 26% (n = 19); cluster II (U. urealyticum): 1; 16% (n = 12)]. Cluster II had a higher rate of polymicrobial findings than cluster I (58% vs 16%; p = 0.005), while subgroup A had the highest rate of concomitant Mycoplasma hominis in the amniotic fluid samples (66%; p = 0.04). In conclusion, Ureaplasma spp. DNA obtained from PPROM consisted of 33 different eSTs of U. spp. DNA. No differences in maternal and neonatal characteristics were found among the phylogenetical subgroups of U. spp. DNA, except for a higher rate of polymicrobial amniotic fluid findings in those with U. urealyticumand the concomitant presence of M. hominis in the amniotic fluid in those with the presence of U. parvum.

Cor triatriatum dexter: an uncommon cause of neonatal cyanosis.

BACKGROUND: Cor triatriatum dexter (CTD) is an extremely rare pathology, with an incidence of < 0.4%. Its main characteristic is a partitioning of the right atrium by the persistence of the embryonic valve of the right sinus venosus. CLINICAL CASE: In this report, we describe the case of a 7-day-old newborn who presented with persistent cyanosis associated with feeding and crying. The diagnosis of CTD was made after an echocardiogram and confirmed using cardiac magnetic resonance imaging. The patient underwent successful surgery on day 14 with a favorable outcome and without complications. CONCLUSION: The importance of our case lies in the identification of rare heart disease as a cause of cyanosis and desaturation in a neonatal patient in the first days of life who did not present signs of heart failure and whose condition improved with supplemental oxygen. We also demonstrate that early diagnosis with echocardiography and surgical resolution resulted in clear clinical improvement and avoided future complications.

INTRODUCCIÓN: El cor triatriatum dexter es una cardiopatía muy rara, caracterizada por la división parcial del atrio derecho en dos cavidades por la persistencia de una membrana que embriológicamente representa la valva derecha del seno venoso. CASO CLÍNICO: En este reporte de caso, presentamos el caso de un neonato en su día 7 de vida que acude a valoración por presentar desaturación persistente con cianosis al llanto. El diagnóstico se realizó con ecocardiograma posterior al cual se decidió la resección quirúrgica de la membrana, procedimiento que fue llevado a cabo el día 14 de vida con éxito sin complicaciones. CONCLUSIONES: La importancia de este caso clínico radica en la identificación de una cardiopatía rara como causa de cianosis y desaturación en un paciente en etapa neonatal, el cual no presentaba datos de compromiso hemodinámico. También se muestra como un diagnóstico y tratamiento quirúrgico oportuno permitieron una resolución de los síntomas sin complicaciones futuras.

Thiamine: An indispensable regulator of paediatric neuro-cardiovascular health and diseases.

The sustainable developmental goals emphasize good health, reduction in preventable neonatal and under-five mortalities, and attaining zero hunger. However, South Asian countries report a higher incidence of neonatal and under-five mortalities when compared to the Western world, many of which are attributed to maternal and perinatal micronutrient deficiencies. Isolated nutrient deficiency in the absence of calorie deficit poses a diagnostic challenge since such deficiencies present with acute multisystemic and enigmatic manifestations. Thiamine (vitamin B1) is a micronutrient of prime importance which exerts indispensable roles in energy metabolism. Deficiency of thiamine can lead to catastrophic consequences. This review provides insight into the biochemical actions of thiamine in energy metabolism, the compromised aerobic metabolism resulting from thiamine deficiency, and the crucial role of thiamine in the proper functioning of the nervous, cardiovascular, and immune systems. The review also explores the acute life-threatening consequences of thiamine deficiencies in neonates and infants and the speculative role of thiamine in other pathologies like encephalopathy, sepsis, and autism spectrum disorders. However, routine assessment of thiamine in pregnant women and neonates is yet to be implemented, due to the lack of affordable and automated diagnostic techniques, and the cost-intensive nature of mass spectrometry-based quantification. CONCLUSION: Physicians are recommended to have a low threshold for suspecting thiamine deficiency especially in vulnerable populations. Laboratory diagnosis of thiamine deficiency needs to be implemented as a standard of care, especially in endemic regions. Further, public health policies on food fortification, mandatory supplementation, and surveillance are imperative to eliminate thiamine deficiency-induced health hazards. WHAT IS KNOWN: • South Asian countries report a higher incidence of neonatal and under-five mortalities, many of which are attributed to maternal and perinatal micronutrient deficiencies. • Preventable causes of neonatal/ infantile deaths include birth factors (low birth weight, birth asphyxia), infectious diseases (pneumonia, diarrhoea, tetanus, tuberculosis, measles, diphtheria, malaria, acute infections), deficiency diseases and genetic diseases (vitamin & mineral deficiencies, IEMs, congenital heart disease, unexplained PPHN, SIDS etc). WHAT IS NEW: • Acute thiamine deficiency presenting as multisystemic syndromes, has unfortunately been a long standing unresolved public health concern. However, accessible surveillance and diagnostic strategies remain elusive in most clinical settings. • Despite decades of reports and emerging guidelines, diagnosis of thiamine deficiency is often missed and policy mandates at national level are yet to be implemented even in endemic countries. • This review provides a comprehensive summary of the biochemical role of thiamine, its key functions and effects on major organ systems, the diagnostic gap, the enigmatic presentation of acute thiamine deficiency, the plausible role of thiamine in other pathologies and the preventive measures at individual and community level.

Implementation of standardized feeding pathways for infants with gastroschisis to improve patient outcomes: A quality improvement project in a level IV surgical NICU.

Gastroschisis is a leading cause of pediatric intestinal failure. Feeding guidelines may lead to improved patient outcomes including decreased time to reach full feeds, a reduction in the duration of parenteral nutrition, and reduced length of stay. However, there is limited evidence on what the ideal feeding guidelines are for this complex gastrointestinal diagnosis. In this quality improvement project, after completing a literature review, we created three pathways based on the complexity of the gastroschisis. We reviewed historical data without a defined feeding pathway/guideline to our newly created pathways in the intervention group. The study included 35 patients with varying degrees of gastroschisis complexity, consisting of 9 current patients (October 2021-December 2022) who were provided with defined feeding pathways and 26 historical patients before the protocol was implemented (January 2015-August 2021). There were no significant differences in the number of days required for full feeds between the two groups. However, the mean duration of parenteral nutrition was 18.9 days (95% CI, -31.8 to -7.0) shorter in the intervention group. Although not statistically significant, the patients in the intervention group had a mean length of stay that was 13.1 days (95% CI, -50.0 to 25.4) shorter than the historical group. The creation of standardized feeding guidelines for the gastroschisis population resulted in a statistically nonsignificant decrease in time to reach full enteral feeds, a statistically significant reduced duration of parenteral nutrition, and a statistically nonsignifiant decreased length of stay.

Immune Biomarkers at Birth Predict Lower Respiratory Tract Infection Risk in a Large Birth Cohort.

Lower respiratory tract infections (LRTIs) remain the leading cause of infant morbidity and mortality worldwide and affect long-term respiratory health. Identifying immunological determinants of LRTI susceptibility may help stratify disease risk and identify therapies. This study aimed to identify neonatal immunological factors predicting LRTI risk in infancy. Cord blood plasma from 191 neonates from the Boston Birth Cohort was analyzed for 28 soluble immune factors. LRTI was defined as bronchiolitis, bronchitis, or pneumonia during the first year of life. Welch's t-test demonstrated significantly higher log10 transformed concentrations of IL-17 and IFNγ in the LRTI group compared to neonates without LRTI in the first year of life (p < 0.05). Risk associations were determined using multivariate survival models. There were 29 infants with LRTIs. High cord blood levels of IFNγ (aHR = 2.35, 95% CI 1.07-5.17), TNF-ß (aHR = 2.86, 95% CI 1.27-6.47), MIP-1α (aHR = 2.82, 95% CI 1.22-6.51), and MIP-1ß (aHR = 2.34, 95% CI 1.05-5.20) were associated with a higher risk of LRTIs. RANTES was associated with a lower risk (aHR = 0.43, 95% CI 0.19-0.97). Soluble immune factors linked to antiviral immunity (IFNγ) and cytokines mediating inflammatory responses (TNF-ß), and cell homing (MIP-1α/b), at birth were associated with an increased risk of LRTIs during infancy.

Physiologically Based Pharmacokinetic Modeling of Vancomycin and its Comparison with Population Pharmacokinetic Model in Neonates.

Vancomycin has a narrow therapeutic window and a high inter-individual pharmacokinetic variability, especially in neonates with fast maturational and pathophysiological changes, that needs individualized dosing. Physiologically based pharmacokinetic (PBPK) model and population pharmacokinetic (PopPK) model are both useful tools in model-informed precision dosing, while the former is under research in application of vancomycin in neonates. This study aimed to develop a PBPK model of vancomycin in adult and pediatric population, and compared it with published PopPK model (priori or Bayesian method) in predicting vancomycin concentration in 230 neonatal patients (postmenstrual age, PMA, 25-45 weeks). The developed PBPK model showed a good fit between predictions and observations. PBPK model and PopPK model are complementary in different clinical scenarios of vancomycin application. The physiological-change description of PBPK model showed a superior advantage in initial dosing optimization. As for subsequent dose optimization, PopPK Bayesian forecasting performed better than the PBPK estimation in neonates. However, initial precision dosing tools for early neonates (with PMA < 36 weeks) still need further exploitation.

Outcome of Nasal continuous positive airway pressure in neonates: A cross-sectional study.

Objective: This study aimed to assess the efficacy of nasal continuous positive airway pressure (CPAP) in term and preterm neonates with respiratory distress by evaluating successful outcomes, identifying factors contributing to treatment failure, and documenting associated complications. Method: A comparative cross-sectional study design was employed. The research was conducted at Combined Military Hospital (CMH) Rawalpindi from November 2022 to July 2023. All consecutive neonates admitted during the specified period with respiratory distress requiring CPAP treatment and meeting inclusion criteria were enrolled. Pre- and post-CPAP respiratory distress levels, relevant biochemical markers, as well as mortality and morbidity rates were documented. Both descriptive and inferential statistical analyses were employed. Results: The mean age of the study cohort was 53.3±85.6 minutes. The average time to initiate CPAP was 82.4 ± 94.7 minutes. Mean gestational age stood at 34.68±2.8 weeks. CPAP was successful in 97% of babies. The low birth weight below 1200grams was the main factor related to failure of CPAP. The mean Downes score decreased from 5.8±1.3 before CPAP to 3.3±1.6 after 12 hours of CPAP and further to 1.85±2 after 24 hours. Significant improvements in Downes score were noted after 24 hours of CPAP usage (p < 0.05) using paired sample T-test. Conclusion: This study affirms the effectiveness of CPAP in addressing neonatal respiratory distress. The utilization of CPAP emerges as a valuable intervention that not only reduces the requirement for invasive ventilation but also exhibits the potential to alleviate morbidity and mortality rates among neonatal populations.