To investigate the effects of maternal glycemic control during pregnancy on early biomarkers of neonatal metabolic syndrome. We prospectively enrolled 130 pregnant women. Based on glycemic control, they were classified into adequate control group (n = 82, including 59 with normal glucose tolerance and 23 with well-controlled GDM) and poor control group (n = 48, GDM with suboptimal control). Neonatal tyrosine, alanine, total carnitine, C18 acylcarnitine, bilirubin, and hypoglycemia incidence were measured. Multivariable linear regression adjusted for confounders, with Bonferroni correction (α=0.01). Compared with the adequate glycemic control group, neonates in the poor glycemic control group exhibited significantly lower levels of tyrosine and alanine (all P < 0.05), and significantly higher levels of total carnitine, C18 acylcarnitine, and bilirubin (all P < 0.05). The incidence of neonatal hypoglycemia was also significantly higher (P < 0.05). There were no significant differences between groups in the exact timing of blood sampling for amino acids or bilirubin (P > 0.05). After adjustment for pre-pregnancy body mass index (BMI), gestational age at delivery, mode of delivery, neonatal sex, maternal age, parity, feeding before blood collection, and thyroid dysfunction, poor maternal glycemic control remained independently associated with decreased neonatal tyrosine (β = --0.335, P = 0.009) and alanine (β = -0.289, P = 0.019), as well as increased total carnitine (β = 0.381, P = 0.003), C18 acylcarnitine (β = 0.348, P = 0.006), and bilirubin levels (β = 0.405, P = 0.002). After Bonferroni correction for multiple comparisons (α = 0.01), tyrosine, total carnitine, C18 acylcarnitine, and bilirubin remained statistically significant, while alanine did not. Poor glycemic control during pregnancy is associated with multiple abnormalities in early neonatal metabolic biomarkers during the first 72 h after birth. Optimizing glycemic control during pregnancy may help mitigate early metabolic disturbances in the neonatal period. Future long-term follow-up studies are needed to determine whether these early biomarkers predict subsequent metabolic syndrome in later childhood or adulthood.
Neonates are highly susceptible to infection, a major cause of neonatal death, given their immature immune system. Comprehensive studies examining multiple immune-response-related proteins in relation to neonatal infection are scarce. We conducted a nested case-control study within the Shenzhen Baoan Birth and Twin (SZBBTwin) cohort, measuring 92 immune-response-related proteins in cord plasma of 149 twins (including 34 discordant twin pairs) with proximity extension assay. All twins were followed for clinical diagnoses of infection from birth until 27 days of age. Wilcoxon rank-sum test was used to determine differentially abundant proteins (DAPs) between infected and noninfected neonates, the predictive performance of which was evaluated by receiver operating characteristic curves, and their functions and pathways were annotated through enrichment analysis. Logistic regression was used to assess the associations between levels of proteins and risk of neonatal infection. Finally, five DAPs (ITGA11, FCRL6, DDX58, SH2D1A, and EDAR) were identified for neonatal infection, and the area under the curve of the five DAPs achieved 0.835 for infection prediction. Enrichment analysis indicated that five DAPs were mainly involved in immune function and cell binding, and they were mainly enriched in the nuclear factor kappa-B pathway. A higher level of ITGA11 was associated with an increased risk of neonatal infection in all twins (OR 3.00; 95% CI [1.33, 6.78]) and discordant twin pairs (OR 5.50; 95% CI [1.20, 25.23]). In conclusion, multiple immune-response-related proteins in cord plasma, particularly ITGA11, are associated with the risk of neonatal infection in twins.
Artificial intelligence and large language models (LLMs) have developed rapidly in recent years and involved in medical education, in addition to clinical care. However, it remains unknown how the performance of LLMs in neonatal resuscitation compares to that of healthcare professionals (HCPs). In this exploratory study, we aimed to investigate and compare the performance of LLMs with those of HCPs on 3 sources of examination questions in the neonatal resuscitation training in Canada and China. In this bi-center study, we evaluated the overall accuracy, accuracy across question types, and reliability of LLMs' (ChatGPT-5 and DeepSeek-R1) responses to neonatal resuscitation questions from workshop in China, NRP® textbook (8th edition), and Kahoot quizzes in Canada. Each LLM was tested three times per question with one-week intervals in August and September, 2025. Comparisons with historical scores of HCPs in the training courses in China (2022-2024) and Canada (2022-2025) were performed. Both LLMs performed comparably to HCPs in Chinese examinations, and showed similar accuracy in NRP® textbook questions with higher scores on multiple-choice than on short answer questions. ChatGPT achieved higher accuracy than DeepSeek and HCPs in the Kahoot quizzes. ChatGPT also had higher accuracy on scenario-based than on non-scenario-based questions in the workshop examination. High reliability of LLMs' responses was found (Fleiss' Kappa>0.89). Both ChatGPT and DeepSeek achieved accuracy comparable to that of HCPs and showed high consistency on selected neonatal resuscitation written examinations. The findings warrant further research to explore their potential integration in neonatal resuscitation training.
Perinatal psychosocial health has gained significant attention due to its impact on maternal and neonatal health outcomes. Elevated rates of mental health disorders during pregnancy and the initial postpartum year, particularly pronounced in low- and middle-income countries (LMICs), have been consistently linked to women's heightened exposure to psychosocial risk factors. In response to this evidence, the current investigation is designed to evaluate psychosocial risk status among pregnant women and to explore its associations with both maternal and neonatal outcomes, employing a convergent mixed-methods design. A convergent parallel mixed‑methods design will be employed for this investigation. The quantitative strand comprises a prospective cohort study that will enroll 260 pregnant women at 12-14 weeks of gestation. Based on their ANRQ‑R total scores, participants will be divided into two groups: those scoring 23 or above (high‑risk) will form the exposed cohort, while those scoring below 23 (low‑risk) will constitute the non‑exposed cohort. Both groups will be followed prospectively until six weeks postpartum. At enrolment, a sociodemographic and obstetric characteristics form will be completed. A second data collection point at 31-34 weeks of gestation will involve administration of the Wijma Delivery Expectancy/Experience Questionnaire (W‑DEQ, version A), the Edinburgh Postnatal Depression Scale (EPDS), and the Pregnancy Experience Scale (PES). Postnatally, within six weeks after birth, the following instruments will be administered: a Maternal and Neonatal Outcomes Checklist, the EPDS, the Childbirth Experience Questionnaire version 2.0 (CEQ‑2), the Postpartum Specific Anxiety Scale Research Short‑Form, the Barkin Index of Maternal Functioning (BIMF), and a measure of Breastfeeding Self‑Efficacy. Running concurrently with the quantitative follow‑up, the qualitative phase will recruit participants through purposive sampling from both high‑ and low‑risk groups. Data will be generated via in‑depth, semi‑structured individual interviews using open‑ended questions, allowing for rich exploration of participants' experiences. Finally, the findings from both the qualitative and quantitative strands will be integrated in the discussion section. Identifying psychosocially vulnerable mothers before the onset of mental health disorders during pregnancy, coupled with a deep understanding of the maternal and neonatal outcomes of these risk factors, can provide a roadmap for designing a healthcare system that preemptively safeguards maternal mental health. Furthermore, this approach can contribute to reducing healthcare system costs through timely screening, early intervention, and the effective management of psychosocial conditions. Contrary to past beliefs, mental health issues during pregnancy are as common as, and sometimes even more prevalent than, in the postpartum period. While pregnancy can be a vulnerable time for mental health, it also provides a unique “window of opportunity” for identifying and treating psychological and social challenges. For a mother who has experienced past trauma, pregnancy offers a chance to form a new, secure, and loving bond with her child—essentially providing a way to “rewrite” her own past experiences. Therefore, the objectives of this study include assessing psychosocial risk levels, determining their impact on maternal and neonatal outcomes, alongside an exploration of women’s perceived experiences of pregnancy, achieved by merging quantitative statistical data with in-depth qualitative accounts.This research uses a multi-phase “mixed-methods” approach in three stages: 1. Quantitative Phase: We will examine how psychosocial risk levels during pregnancy relate to maternal outcomes (such as the pregnancy and childbirth experience, and depression) and newborn outcomes (such as low birth weight); 2. Qualitative Phase: We will conduct in-depth, personal interviews with women to understand their individual stories and perceptions; 3. Mixed Phase: We will merge the statistical findings with the personal insights from the interviews to create a complete and clear picture of the situation.Given the lack of multifaceted screening tools and the critical gaps in prenatal mental health care, this research holds significant importance. It emphasizes the need for a proactive healthcare roadmap to safeguard maternal mental health, aligning with the goal of preventing adverse outcomes and ensuring comprehensive support for both mothers and newborns.
Acute kidney injury (AKI) is common among neonates in the intensive care unit and has been linked to abnormal neurodevelopment, yet long-term effects on brain structure remain uncharacterized. In this secondary analysis, we compared brain white matter integrity, measured by fractional anisotropy (FA) on 3T MRI, in children ages 5-12 years born preterm with (n=5) versus without (n=10) a history of neonatal AKI. Contrary to our hypothesis, children with prior neonatal AKI showed higher FA across seven white matter regions in unadjusted analyses. After adjustment for sex, birth weight, and age at MRI, the AKI group retained significantly greater FA in the corticospinal tract (β=0.7, 95% CI 0.09-1.31) and superior frontooccipital fasciculus (β=0.68, 95% CI 0.02-1.34). Because elevated FA may reflect compensatory glial responses rather than improved neurological function, these findings suggest neonatal AKI may have lasting, complex effects on white matter microstructure. Larger studies pairing neuroimaging with neurocognitive assessment are needed.
Congenital toxoplasmosis (CT) is a vertically transmitted infection with a variable clinical spectrum, ranging from asymptomatic infection at birth to severe neurological and ocular sequelae. While the classic triad of hydrocephalus, intracranial calcifications, and chorioretinitis is well characterized, isolated neonatal hyperbilirubinemia as the initial presenting feature is uncommon and may delay diagnosis. We report a case of CT in a Chinese neonate who presented with jaundice and was subsequently found to have subclinical active chorioretinitis, cerebral edema, and bilateral central auditory pathway dysfunction. The case also illustrates therapeutic challenges related to the availability of first-line anti-parasitic agents. A 9-day-old term male infant was admitted for persistent jaundice. He was born at 39 + 4 weeks' gestation, with a prenatal history notable only for maternal cat exposure and treated hypothyroidism. Initial serological testing at the referring hospital revealed positive Toxoplasma gondii IgM and IgG. After transfer, two consecutive blood metagenomic next-generation sequencing (mNGS) tests detected T. gondii DNA (reads: 6 and 7). The combination of negative first-trimester maternal serology, postpartum maternal IgM/IgG positivity, neonatal IgM positivity, and repeated detection of T. gondii DNA in neonatal blood strongly supported congenital toxoplasmosis. Cerebrospinal fluid (CSF) analysis showed pleocytosis and elevated protein, while CSF mNGS was negative, possibly reflecting low pathogen burden or compartmentalized infection. Further evaluation demonstrated bilateral active chorioretinitis on fundoscopic examination, abnormal brainstem auditory evoked potentials consistent with bilateral central auditory pathway dysfunction, and brain MRI showing cerebral edema with punctate hemorrhages. Due to initial unavailability of pyrimethamine, azithromycin followed by trimethoprim-sulfamethoxazole was administered; however, no clear improvement in CSF inflammatory indices was observed during this period. After initiation of standard therapy with pyrimethamine, sulfadiazine, and folinic acid, the patient demonstrated rapid clinical improvement and radiological resolution of brain lesions on follow-up MRI, with marked improvement of chorioretinal scars. Clinicians should consider congenital toxoplasmosis in neonates with unexplained jaundice, even in the absence of classic clinical manifestations. Comprehensive multi-organ evaluation, including neuroimaging, ophthalmologic examination, and auditory testing, is essential for early disease characterization. Standard pyrimethamine-sulfadiazine-folinic acid therapy may be associated with better clinical and radiological outcomes and should be used when available. Long-term multidisciplinary follow-up is necessary to monitor potential sequelae.
The neonatal period is a critical time for both the newborn and the parents, as they transition into parenthood. Mothers with babies admitted to neonatal intensive care units (NICUs) often experience emotional distress, uncertainty, separation from their babies, and disruption of expected maternal roles. In low-resource settings such as Northern Uganda, where neonatal care and psychosocial support services remain limited, little is known about the experiences of mothers with babies admitted to the NICU. This study explored the lived experiences of mothers with babies admitted to the NICU of Lira Regional Referral Hospital in Northern Uganda. A descriptive phenomenological study was conducted at a public regional hospital in Northern Uganda (PRRH). We purposively selected 10 mothers whose babies had been admitted to the NICU for at least three days. Data were collected through phenomenological in-depth interviews. Interviews were audio-recorded, transcribed verbatim, and analyzed using Braun and Clarke's thematic analysis framework. Four major themes emerged from the analysis: emotional grief regarding baby's hospitalization/admission needs, burden of a baby's hospitalization, mother's satisfaction with care given by healthcare workers and altered motherhood role and support systems. Mothers described intense emotional distress characterized by fear, uncertainty, hopelessness, and disruption of maternal expectations. Financial hardship, prolonged hospitalization, and separation from family further intensified their experiences. Despite these challenges, many mothers expressed appreciation for the compassionate care provided by healthcare workers and relied on spirituality and hope as coping mechanisms. Mothers' experiences were shaped by communication from health workers, the baby's clinical condition, hospital requirements, and the availability of interpersonal support. Improving communication, ensuring availability of essential supplies, and strengthening interpersonal support may improve mothers' experiences during NICU admission.
The basal ganglia and thalamus are key nodes in subcortico-cortical loops involved in sensory, motor, and cognitive function. In adults, posterior regions of the subcortex link to cortical sensorimotor networks and anterior regions link to association networks. Alterations in the size, strength, and selectivity of these subcortical regional network representations are implicated in several neuropsychiatric disorders, many of which originate early in development. However, the organization of these network representations at birth remains incompletely understood, limiting our ability to devise normative and atypical developmental models of subcortico-cortical interactions. Using resting-state fMRI, we characterized the size, strength, and selectivity of cortical network representations in the basal ganglia and thalamus in a set of neonates (n=261) and compared results to children (age range 9-11 years, n=69) and adults (n=120). We found that the broad anterior-posterior organization of the subcortex is present at birth, yet representations of somatomotor networks were larger at birth compared to children and adults (p<0.001). The strength and selectivity of subcortico-cortical functional connectivity (FC) exhibited interactions between age group and network (all p<0.001), such that subcortical representations of sensorimotor networks exhibited stronger FC and higher selectivity in neonates, while subcortical representations of association networks exhibited stronger FC and higher selectivity in older cohorts. In parallel, data-driven clustering revealed areas with integration of multiple networks in the neonatal subcortex. These results suggest that subcortico-cortical FC evolves over development largely in a sensorimotor-association manner and provide a baseline for normative and disordered subcortical development. The basic anterior-posterior layout of association to sensorimotor network representation in the basal ganglia and thalamus is present at term birth.Sensorimotor systems are overrepresented in neonates compared to children and adults.Sensorimotor representations exhibit greater functional connectivity strength and selectivity than association representations at birth, while association representations are stronger and more selective than sensorimotor representations in adults.The neonatal subcortex exhibits substantial integration of multiple cortical networks.
This report describes the imaging findings of a neonatal case of horseshoe lung (HL) associated with multisystem malformations. The patient was a premature female neonate who presented with respiratory distress after birth. Physical examination revealed anal atresia with a rectovestibular fistula. Imaging examinations revealed multisystem malformations, including HL with abnormal bronchial branching and pulmonary hypoplasia, scimitar syndrome (infantile type), complex cardiovascular malformations, duodenal obstruction, and multiple vertebral anomalies. The application of multiple imaging modalities enabled comprehensive evaluation of the patient's condition and provided a basis for subsequent treatment and prognosis assessment.
This study aimed to evaluate the impact of Active Perinatal Treatment (AT) for 22-week live births on national 1-year survival trends to guide clinical decisions and counseling. We utilized U.S. natality data (2019-2022) to identify a cohort of non-anomalous, singleton live births at 22 weeks' gestation. The cohort was divided into two groups: AT and Non-Active Perinatal Treatment (Non-AT). AT was defined as receiving more than one of the following: Antenatal corticosteroids, cesarean delivery, neonatal intensive care unit (NICU) admission, neonatal antibiotics, surfactant, or mechanical ventilation (immediate or for >6 hours). Maternal and neonatal outcomes were compared between the two groups, and a Cox proportional hazards model adjusted for maternal age, race, education, prepregnancy medical history, and birth weight was used to assess adjusted hazard ratios (aHRs) for mortality within the first year of life. A subanalysis was performed to compare the neonatal and postneonatal survival rates among the two groups and over time. Of the 4,994 live births at 22 weeks, 2,769 (55.4%) received AT, and 2,225 (44.6%) were in the Non-AT group. One-year survival rate for the AT group was estimated at 34% compared with 8.6% in the Non-AT group. AT reduced the mortality hazard by 63% during the first year of life (aHR = 0.37; 95% CI: 0.34-0.39, p < 0.001). From 2019 to 2022, AT use increased from 49.8% to 63.9%, paralleled by improved survival (p < 0.003). Neonatal and postneonatal survival rates were higher with AT compared with the Non-AT for each year (p < 0.001). Active treatment at 22 weeks significantly improves the 1-year survival. Its rising national use reflects growing clinical acceptance and highlights a potential shift in the threshold of viability in U.S. neonatal care. · U.S. national data were used to evaluate one-year survival rates among infants born at the threshold of viability who received proactive care.. · One-year survival was significantly higher for 22-week live births that received active perinatal treatment.. · Active treatment was associated with a 63% reduction in the risk of one-year mortality among live births at 22 weeks of gestation.. · The study observed an increase in the utilization of active treatment for 22-week live births in the U.S. between 2019 and 2022..
 Expansion of special newborn care units (SNCUs) in India has improved neonatal survival. However, information regarding post-discharge suspected developmental delay outcomes among SNCU graduates remains limited, particularly in rural settings.  This study aimed to determine the prevalence of suspected developmental delay among infants ≤12 months of age discharged from an SNCU through screening and to identify associated neonatal risk factors.  This hospital-based prospective follow-up study included 113 infants discharged from the SNCU of a rural tertiary care hospital in North India. Suspected developmental delay was assessed using the Trivandrum Developmental Screening Chart (TDSC), a validated screening tool. Infants who screened positive were considered to have suspected developmental delay. Maternal and neonatal risk factors were recorded. Associations were analyzed using chi-square/Fisher's exact test and multivariate logistic regression.  Suspected developmental delay based on TDSC screening was identified in eight of 113 infants (7.1%). On univariate analysis, low birth weight (<2.5 kg), prematurity (<37 weeks), maternal hypothyroidism, and neonatal resuscitation were significantly associated with suspected developmental delay (p<0.05). On multivariate analysis, neonatal resuscitation (adjusted odds ratio (OR) 4.12; 95% confidence interval (CI) 1.18-14.32; p=0.026) and low birth weight (adjusted OR 3.21; 95% CI 1.05-9.81; p=0.041) remained independent predictors.  Approximately one in 14 infants discharged from the SNCU showed suspected developmental delay based on screening at one year of age. Neonatal resuscitation and low birth weight were independent predictors. These findings highlight the need for structured developmental screening and follow-up of high-risk neonates within primary care and rural health systems.
Sleep-wake regulation and comfort are essential for neurodevelopment and physiological stability in newborns in neonatal intensive care units, yet evidence on non-pharmacological interventions such as automatic infant swings is limited. This is a study protocol which outlines a randomized controlled crossover study that aims to evaluate the effects of an automatic infant swing on sleep-wake cycles, comfort behaviours and physiological parameters in newborns in neonatal intensive care units. The study protocol was designed as a single-blind randomized controlled crossover trial and will be conducted in the neonatal intensive care unit of a state hospital in Central Anatolia, Turkey, including newborns born between 35 and 42 weeks of gestation. Based on G*Power analysis, a total sample of 40 infants will be included and randomly assigned to group A (n = 20) or group B (n = 20) using block randomization. Newborn sleep-wake cycles will be assessed using the Bispectral Index (BIS) under two conditions: a cot bed and an automatic infant swing. Measurements will be performed four times, twice during the day and twice at night, each lasting 60 min. During each measurement period, comfort behaviours and physiological parameters will be recorded at 0, 30 and 60 min. The measurements of the study outcomes will be evaluated using the 'Information Form', 'Comfort Behaviour Scale (COMFORTneo)', 'Sleep-Wake Cycle Tracking Chart' and 'Physiological Parameters Tracking Chart' developed by the researchers. This protocol will evaluate the effects of an automatic infant swing on newborns' sleep-wake cycles measured by BIS, with comfort behaviours and physiological parameters as secondary outcomes. This study protocol may contribute to neonatal intensive care nursing practice by providing evidence regarding the effects of automatic infant swings on newborns' sleep-wake cycles, comfort behaviours and physiological parameters. The study protocol was registered on ClinicalTrials.gov (NCT07284303).
Neonates have the highest incidence of thrombosis among pediatric populations, and preterm infants are at a high risk of venous thrombosis, with its risk factors remaining inconclusive and treatment criteria remaining ununified. This study aimed to explore the high-risk factors for venous thrombosis in preterm infants with varying gestational ages and catheterisation types, and to clarify the clinical characteristics, treatment strategies, and short-term prognosis of neonatal venous thrombosis, to provide evidence for clinical decision-making. A retrospective cohort study was conducted on 282 preterm infants admitted to the Neonatal Intensive Care Unit of Peking University Third Hospital from January 2014 to December 2025, including 94 cases in the thrombosis group and 188 cases in the control group. Clinical data, including maternal prenatal information, infant basic information, diagnosis and treatment course, catheter-related information, and thrombosis-related details, were collected from the electronic medical record system. SPSS 27.0 software was used for statistical analysis using the Kruskal-Wallis test, Student's t-test and Mann-Whitney U test for continuous variables; chi-square test or Fisher's exact test for categorical variables; and univariate and multivariate logistic regression models and Firth's penalised likelihood logistic regression analyses were applied to identify independent risk factors for venous thrombosis in preterm infants. The incidence of venous thrombosis was 0.45% in all hospitalised neonates and 1.0% in hospitalised preterm infants, with no significant differences in baseline data such as gestational age and birth weight between the two groups (P > 0.05). Multivariate logistic regression analysis showed that right- and left-sided lower extremity PICC placement were independent risk factors for venous thrombosis in all preterm infants (P = 0.000 and 0.007, respectively). Maternal anticoagulant or antiplatelet agents use during pregnancy was a clinical predictor(P = 0.046). Stratified analysis by gestational age revealed that right lower extremity PICC placement(P = 0.000) was an independent risk factor for very preterm infants (gestational age <32 0/7 weeks), and PICC placement (P < 0.001) was also an independent risk factor for moderate-to-late preterm infants (32 0/7 weeks ≤ gestational age <37 0/7 weeks). Among all thrombotic groups, 96%(90/94) were associated with central venous catheterisation, including 22 cases of portal vein thrombosis (related to umbilical venous catheterisation) and 68 cases of extremity venous thrombosis (related to PICC placement). The median time from catheterisation to thrombosis was 5 (3.8, 8.0) days, with 59% were deep vein thrombosis and 59% were occlusive thrombosis. Only 34% of infants had clinical manifestations, and the detection rate of asymptomatic thrombosis increased with routine vascular ultrasound application. A total of 40% of patients received pharmacotherapy (mainly nadroparin calcium, supplemented with rt-PA), with 5% discontinuing medication due to active bleeding. For central venous catheters that were no longer in use, superficial vein thrombosis was managed by immediate catheter removal without anticoagulation. For deep vein thrombosis, anticoagulation was administered for at least 3 days, followed by catheter removal after follow-up imaging confirmed thrombus resolution or stabilisation. No thromboembolic events occurred during this process. After treatment, 98% of infants improved and were discharged; 65% of thrombi completely resolved, and 21% reduced in size before discharge, with a median resolution/reduction time of 17 (7, 31) days, and no extremity functional impairment was observed in any case. Compared with the PICC-related thrombosis group, the UVC-related thrombosis group was characterised by significantly higher birth weight (P = 0.010), a shorter interval between catheter placement and thrombosis (4.0 vs. 6.0, P = 0.019), and a shorter duration of hospitalisation (32.5 vs. 53.9, P = 0.003). Lower extremity PICC placement is a core independent risk factor for venous thrombosis in preterm infants, with maternal anticoagulant use during pregnancy perhaps being a clinical predictor for all preterm infants. Neonatal venous thrombosis is mostly catheter-related, with a high proportion of asymptomatic cases, and routine vascular ultrasound can improve its detection rate. Individualised pharmacotherapy based on clinical manifestations and thrombus characteristics is associated with a favourable short-term prognosis, and timely adjustment of an abnormal catheter position is crucial for reducing thrombosis risk. Long-term follow-up is still needed for preterm infants with venous thrombosis to monitor for late adverse outcomes.
Neonatal pneumopericardium is a rare form of air leak syndrome associated with high morbidity and mortality. With advances in neonatal care, the incidence of pneumopericardium has decreased, as with other air leak syndromes; however, most cases occur in premature infants with a history of respiratory distress and mechanical ventilation. Pneumopericardium should be considered in the differential diagnosis of newborns experiencing sudden respiratory distress. Early diagnosis and appropriate treatment can significantly reduce mortality. This case report presents the management of isolated pneumopericardium using ultrasound-guided pericardiocentesis, which was detected after sudden clinical deterioration in a premature female infant born at 28 gestational weeks and followed up on mechanical ventilation. Recognition and prompt intervention by neonatal intensive care unit physicians significantly impact the patient's prognosis.
We aimed to assess neonatal survival and identify predictors of mortality among infants admitted to a tertiary hospital in Iran between 2016 and 2022. A retrospective cohort study was conducted on 7,255 neonates admitted to a tertiary hospital in Iran. Overall neonatal and preterm mortality rates were 6.6% and 9.1%, respectively, with a declining trend across various medical conditions. Multiple Cox regression analysis revealed several predictors of death as gestational age, birth weight, APGAR scores, congenital defects, sepsis, respiratory disorders, intervention treatments, and antibiotic administration history. Implications for Practice: Although survival rates have improved, neonatal mortality in Iran remains a concern. The leading causes of death-congenital anomalies, sepsis, and respiratory disorders-highlight the need for strengthened antimicrobial stewardship and infection control. Managing invasive procedures is essential to prevent hospital-acquired infections. Further studies are needed to clarify the causal relationship between multiple antibiotic regimens and neonatal survival.
Long-chain fatty acid oxidation disorders (LcFAODs) are rare inherited disorders associated with impaired energy metabolism and increased risk of metabolic decompensation during catabolic stress. With improved diagnosis and care, affected women reach reproductive age, making pregnancy management an emerging clinical challenge. We conducted an international, web-based survey among 55 metabolic centers from 21 countries to assess clinical management of pregnancies in women with lcFAODs focusing on management strategies rather than pregnancy outcomes. The 23-item questionnaire addressed preconception counseling, monitoring strategies, dietary management, peripartum care, postpartum follow-up, and neonatal management. Among respondents, 65% had managed pregnancies in women with lcFAODs, reporting 131 cases, most commonly in CPT2 (n = 52) and VLCAD (n = 44) deficiencies. Preconception counseling and genetic consultation were widely recommended (>85%). Core management principles included dietary adaptation with restriction of long-chain fatty acids, supplementation with medium-chain triglycerides, and prevention of catabolism. Marked inter-center variability was observed in monitoring frequency, biochemical parameters, and follow-up intensity. Creatine kinase was the most used biochemical marker for monitoring metabolic stability. Multidisciplinary care was endorsed but inconsistently implemented, with approximately half of the centers reporting structured multidisciplinary meetings. Individualized peripartum plans were nearly universal, and delivery in specialized centers was generally recommended. Pregnancy in women with lcFAODs is generally considered feasible and safe under specialist metabolic and obstetric care. However, management remains highly heterogeneous, particularly regarding monitoring and multidisciplinary structures. These findings highlight the need for international consensus and standardized care frameworks to optimize maternal and neonatal outcomes.
Neprilysin (NEP) is a zinc-dependent metalloprotease targeted in heart failure therapy to prevent it degrading circulating cardioprotective vasoactive peptides. NEP can also cleave sarcolipin (SLN), the skeletal- and atrial muscle-specific micropeptide regulator of the sarcoplasmic reticulum Ca 2+ -ATPase (SERCA). A direct pathophysiological role of NEP in ventricular muscle has not been established. Proteomics and immunoblot analysis of human myocardial specimens were used to quantify NEP abundance in failing and non-failing hearts. Heterologous protein expression and biochemical binding assays assessed NEP-mediated cleavage of phospholamban (PLB) and its impact on PLB-SERCA interactions. Functional consequences of NEP expression or inhibition were evaluated in neonatal rat ventricular myocytes and in a human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model of heart failure. We observed increased NEP abundance in failing human myocardium relative to non-failing controls. We demonstrated that NEP cleaves phospholamban (PLB), disrupting PLB-SERCA interactions. Mutation of PLB (V49A), prevented NEP cleavage and preserved PLB-SERCA binding, indicating V49 is critical for NEP substrate recognition. In neonatal rat ventricular myocytes, NEP expression was associated with faster Ca 2+ transient decay kinetics and increased SR Ca 2+ load, consistent with reduced SERCA inhibition. Inhibition of NEP in a hiPSC-CM heart failure model attenuated the hypertrophic transcriptional responses and reversed Ca 2+ -transport dysregulation. These findings implicate increased NEP expression in the sarcoplasmic reticulum of cardiomyocytes as previously unrecognized maladaptive consequence of heart failure contributing to cardiac dysfunction. In this novel pathophysiological mechanism, increased NEP results in PLB cleavage and loss of regulation of SERCA. While this may relieve SERCA inhibition and augment cellular Ca 2+ handling, loss of PLB chronically disrupts heart's dynamic response to adrenergic stress, changing heart rate, or other physiological challenges. The data provide new insight into the cardioprotective effects of pharmacological NEP inhibition in clinical practice, reveal a novel mechanism of action of neprilysin inhibition in cardiomyocytes and may help inform future therapeutic strategies for patients with heart failure.
The Bacillus Calmette-Guérin (BCG) vaccine, a live-attenuated derivative of Mycobacterium bovis, has long been central to global tuberculosis prevention. Although it protects well against severe childhood TB, its efficacy against adult pulmonary TB is variable. At the same time, epidemiological and clinical observations suggest that BCG may reduce all-cause mortality and protect against infections beyond TB. Randomised trials have reported lower neonatal all-cause mortality and fewer sepsis-related deaths, supporting the idea of broader immunological benefits. These heterologous effects are proposed to be derived from trained immunity, a form of functional reprogramming of innate immune cells driven by epigenetic and metabolic changes. In some settings, BCG may also induce trained tolerance, leading to a more suppressive immune state, based mainly on animal and in vitro evidence. Clinically, intravesical BCG is an established local immunotherapy for non-muscle-invasive bladder cancer, with current evidence and emerging data suggesting that its effects may extend beyond the bladder through systemic immune training. However, repurposing BCG for other cancers, non-oncological autoimmune diseases, and respiratory tract infections remains established in experimental animal models but is represented with mixed efficacy accompanied by inconclusiveness in human trials and mostly in preclinical or early-phase evidence. Major barriers to translation include strain variability, lack of standardised dosing, uncertain durability, and unresolved long-term safety concerns. Future progress will depend on engineered BCG derivatives, improved delivery systems, rational combination therapies, and well-designed controlled clinical trials.Methodology: Literature was identified through searches of PubMed, Google Scholar, and the Cochrane Library, from database inception to 2026, with a primary focus on studies published between 2011 and 2026. The Bacillus Calmette-Guérin (BCG) vaccine was developed over a century ago, in 1921, to combat tuberculosis. Beyond its primary role, researchers are uncovering its capacity for “trained immunity” a form of innate immune memory. This process involves the functional reprogramming of the body’s natural defenses, which may allow them to respond to a diverse spectrum of pathogens and diseases.Clinical observations have established that BCG administration may reduce neonatal mortality from non-specific infections, such as sepsis, by enhancing the underlying immune reprogramming and granulopoiesis. This broad-spectrum immunomodulation remains investigational and preclinical for oncological applications with mixed and negative results. While BCG is already a foundational immunotherapy for non-muscle-invasive bladder cancer, emerging evidence suggests it possesses epigenetic reprogramming potential that may work to some extent in fighting respiratory tract infections and to some extent slow down progression of autoimmune conditions, including type 1 diabetes and multiple sclerosis, with mixed/biased outcomes.However, the transition from successful preclinical models to widespread clinical use requires addressing several complex variables. These include the nuances of strain variability, standardized dosing protocols, and the long-term systemic safety of these therapies. The future of BCG-based vaccines lies in the development of engineered derivatives and novel delivery mechanisms designed to optimize this “trained” response.For patients and advocates, this research represents a noble pursuit: repurposing the BCG vaccine by overcoming translational challenges and by bridging a century of vaccine history with modern epigenetic science, we can enter a new era of multi-targeted disease prevention and treatment.Methodology: Literature searches were conducted in PubMed, Google Scholar, and the Cochrane Library, with additional screening of relevant reviews and reference lists from independent journals and reputable scientific websites, from database inception to 2026, to identify English-language articles, with a primary focus on recent developments from 2011 to 2026. while integrating a few from foundational records of earlier years. Search terms included combinations of “Bacillus Calmette-Guérin,” “BCG,” “trained immunity,” “innate immune memory,” “heterologous effects,” “epigenetic reprogramming,” “metabolic reprogramming,” “histone modification,” “lactylation,” “tolerance,” and disease-specific terms such as “tuberculosis,” “bladder cancer,” “autoimmunity,” and “viral infection,” chosen to capture the major biological mechanisms, clinical applications, and conflicting or context-dependent outcomes of BCG-induced immune modulation.
Respiratory syncytial virus (RSV) is the leading cause of hospital admission for lower respiratory infection in infants worldwide, with more than 95% of deaths occurring in low-income and middle-income countries. Predictors of adverse outcomes following RSV hospitalisation remain poorly defined. We aimed to identify clinical and anthropometric predictors of mortality among infants admitted with RSV pneumonia and to assess changes in mortality over a 25-year surveillance period. In this retrospective cohort study, we analysed 25 years of paediatric surveillance at Kilifi County Hospital, Kilifi, Kenya, spanning 25 successive RSV seasons. Neonates (aged <28 days) and post-neonatal infants (aged 28 days to 12 months) admitted with WHO-defined pneumonia were tested for RSV and demographic, anthropometric, and clinical data were recorded at admission. The primary outcome was in-hospital death among infants admitted with RSV pneumonia. Predictors of mortality were identified using random-forest and multivariable logistic regression, and temporal trends in mortality and anthropometric status were examined. Of 75 482 admissions of infants to Kilifi County Hospital between Jan 1, 2001, and July 13, 2025, 19 299 (25·6%) met WHO pneumonia criteria and 2745 (22·7%) had RSV. Of these infants, 2390 (87·1%) were post-neonatal, of whom 58 (2·4%) died in hospital with 44 (76%) deaths within 7 days of admission. Mortality was independently associated with congenital heart disease (odds ratio 3·51 [95% CI 1·37-8·97]), severe undernutrition (per 1-unit reduction in weight-for-age Z score: 1·59 [1·28-1·99]), and hypoxaemia (per 1% decrease in peripheral oxygen saturation: 1·05 [1·03-1·08]). 38 (70·4%) of 54 infants with RSV who died in hospital had a mid-upper arm circumference below the severe acute malnutrition threshold of 11·5 cm. There was no evidence of a sustained decline in RSV-associated in-hospital mortality or improvement in anthropometric status over the 25-year study period. RSV mortality in Kenyan infants remains high and has not declined over 25 years. Severe undernutrition and congenital heart disease identify infants with RSV who are at the highest risk of in-hospital death. These findings highlight the role of chronic anthropometric deficits in RSV outcomes and support targeted nutritional interventions to reduce mortality. Bill & Melinda Gates Foundation and Wellcome.