The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Neonatal hyperbilirubinemia (HB) is universally screened in Italy to reduce the risks of subsequent neurological damage. The 2022 American Academy of Paediatrics revised guidelines set higher phototherapy thresholds and offer follow-up recommendations that ultimately reduce HB overtreatment in newborns born at ≥ 35 weeks' gestational age. While assessing the implementation of AAP guidelines at our centre, we compared the clinical and economic outcomes between the AAP 2022 guidelines and current Italian recommendations. We retrospectively applied the American guidelines to newborns managed according to current Italian recommendations, born at our centre between November 2024 and February 2025. Clinical characteristics, bilirubin levels, and interventions were recorded. The Institutional Treasury provided healthcare costs for hospitalisation and interventions. Clinical decisions and subsequent costs were compared. Nine-hundred and four newborns (50% females, median gestational age 39 weeks) were enrolled. Forty-eight (5.3%) patients presented bilirubin-induced risk factors. The bilirubin level informing a clinical decision was performed at a median of 51 (interquartile range 44-58) hours-of-life. AAP guidelines potentially reduced phototherapy by 69.8% (p < 0.001), accounting for a 98 bed-days reduction. Post-discharge bilirubin checks increased by 37.9% (p = 0.004). A 4-month reduction of 16,591.58 € in variable costs and a significant improvement in resource rationalisation were calculated. The AAP 2022 guidelines potentially reduce HB treatment and shift bilirubin surveillance to the outpatient department, enhancing neonatal care efficiency and reducing healthcare costs. These analytical outcomes encouraged the adoption of the AAP guidelines at our centre. Longitudinal surveillance will clarify the safety and actual extent of this change of reference guidelines in our practice. • The risk of bilirubin-induced neurological damage (BIND) in healthy term and near-term newborns has been overestimated in the past. The AAP revised its hyperbilirubinemia guidelines, providing higher hourly bilirubin thresholds for newborns without risk factors for BIND. • Despite reports on the safety and efficacy of the AAP 2022 guidelines, their implementation was not officially encouraged in Italy, making their adoption a choice to be evaluated at a facility level. • Simulation on retrospective data of AAP 2022 guidelines promises a reduction in healthcare costs and rationalisation of healthcare system resources. • The favourable cost-effectiveness analysis prompted the adoption of AAP 2022 guidelines at our centre. Longitudinal surveillance will help clarify the actual extent of economic impact and to assess real-life safety and efficacy of the guidelines.
Antenatal opioid exposure is associated with adverse neurodevelopmental outcomes and smaller brain volumes, but the effects of opioids on newborn cortical folding maturation have not been defined. The Advancing Clinical Trials in Neonatal Opioid Withdrawal Outcomes of Babies With Opioid Exposure (OBOE) Study is a multisite prospective longitudinal cohort study examining the association of antenatal opioid exposure with brain maturation and outcomes in newborns. To compare cerebral cortical folding in newborns exposed to opioids vs nonexposed controls. In this cohort study, full-term newborns from the OBOE study with antenatal opioid exposure and nonexposed controls were recruited at 4 US sites, including obstetric clinics, maternal substance use treatment programs, and birth hospitals, from August 5, 2020, to December 28, 2023. Data analysis was performed from August 19, 2020, to March 25, 2026. Newborn opioid exposure, including opioid-only and polysubstance exposure as well as exposure to specific opioids. Nonsedated T2-weighted magnetic resonance imaging (MRI) data were acquired via harmonized protocols, and 3D brain images were segmented and parcellated using the Developing Brain Region Annotation With Expectation-Maximization pipeline. The inner cortical gray matter surface was used to measure cortical folding across the frontal, parietal, temporal, and occipital lobes. Group differences between opioid-exposed and nonexposed newborns were compared via analysis of covariance, adjusting for postmenstrual age at MRI, sex, birth weight, maternal age, smoking status, and education level. A total of 259 newborns (mean [SD] gestational age at birth, 39.1 [1.0] weeks; 145 [56.0%] male) were included in the analysis, of whom 164 had antenatal exposure to opioids and 95 were nonexposed controls (mean [SD] postmenstrual age at MRI, 42.8 [2.2] and 42.9 [2.0] weeks, respectively). Compared with nonexposed controls, newborns who had been exposed to opioids had significantly decreased sulcal depth in the frontal (difference, -0.11 mm [95% CI, -0.20 to -0.02 mm]), parietal (difference, -0.19 mm [95% CI, -0.31 to -0.07 mm]), and global (difference, -0.09 mm [95% CI, -0.18 to -0.01 mm]) regions, as well as decreased surface area in the frontal (difference, -1048 mm2 [95% CI, -1497 to -598 mm2]), parietal (difference, -501 mm2 [95% CI, -834 to -168 mm2]), temporal (difference, -422 mm2 [95% CI, -682 to -162 mm2]), occipital (difference, -232 mm2 [95% CI, -439 to -26 mm2]), and global (difference, -2185 mm2 [95% CI, -3327 to -1043 mm2]) surfaces. Compared with controls, newborns exposed to methadone showed larger reductions in frontal, parietal, and global surface areas than those exposed to buprenorphine, with parietal surface area significantly reduced only in the methadone-exposed group (difference, -656 mm2 [95% CI, -1111 to -202 mm2]). Newborns with polysubstance exposure had significantly reduced sulcal depth in the frontal, parietal, and global surfaces, as well as reduced surface area across all lobes compared with controls, whereas opioid-only exposed newborns showed fewer significant differences from controls, with reduced parietal sulcal depth and decreased frontal and global surface areas. In this cohort study, newborns with antenatal exposure to opioids had reduced cerebral cortical sulcal depth and surface area compared with nonexposed controls, with greater reductions among newborns exposed to methadone compared with those exposed to buprenorphine, and in newborns with polysubstance exposure compared with those with opioid exposure only. Ongoing serial MRI and long-term follow-up are under way to assess the impact of these early cortical maturational differences on later neurodevelopment and behavior.
Parenting an infant in the neonatal intensive care unit (NICU) can be highly stressful, undermine parental confidence and minimise involvement in infant care. Enhancing parental self-efficacy is therefore crucial to promoting active engagement and supporting positive child outcomes. This study aims to identify the psychosocial needs (emotion regulation and stress management) of NICU parents and examine the factors that influence their engagement in infant care. It also seeks to determine whether higher levels of parental self-efficacy are associated with greater engagement and collaboration with healthcare providers (HCPs) and a shorter NICU stay. A mixed-methods study will be conducted at the Montreal Children's Hospital's Level III NICU located in Quebec, Canada. Parents (ie, mothers and, when available, their partners) will be recruited during their infant's hospitalisation. Participants will complete a set of self-report questionnaires measuring parental engagement, self-efficacy, parent-infant attachment, mental health, perceived stress and social support. Additionally, one parent per family will be invited to participate in a qualitative interview to discuss their experience in the NICU. Qualitative data will be analysed thematically using NVivo 12 to identify key themes, and statistical analyses will be conducted using RStudio to determine which factors are most strongly associated with parental engagement and their interactions with the clinical team. Finally, HCPs will be invited to assist and participate in a qualitative interview regarding their perspectives on the NICU environment and the study's impact on the unit (ie, reduction in HCP burden due to increased parental engagement). Findings from this study will offer valuable insights to inform future clinical strategies aimed at enhancing parental engagement and self-efficacy in the NICU. These outcomes may contribute to improved neonatal outcomes, parental mental health and the advancement of evidence-based, family-centred care policies. The protocol was approved by the Montreal University Health Centre's (MUHC) Research Ethics Board (2025-9392). Findings derived from this study have the potential to optimise parental engagement in the NICU to promote family resilience and child well-being. Our study protocol aims to underscore the critical role of self-efficacy and other key psychosocial factors, such as lower parental stress and higher emotion regulation, in promoting parental engagement and collaboration within the NICU. We anticipate that higher levels of self-efficacy will correlate with parental well-being, increased caregiving engagement (ie, basic baby care, improved communication with NICU staff) and enhanced parent-infant bonding. These findings may support the development of structured interventions that empower parents and streamline provider-parent collaboration. In clinical practice, these insights can guide the integration of tailored parental support programmes to optimise discharge preparation and reduce provider burden by promoting shared caregiving responsibilities. Future initiatives could build further on this model to guide institutional policies that aim to prioritise parental empowerment (ie, greater self-efficacy and engagement) as a fundamental pillar of neonatal care.
Our study aimed to investigate the experiences of adolescents and young adults (AYAs) with cancer from racially/ethnically diverse and/or 2SLGBTQIA + communities within the Canadian healthcare system to identify areas for improvement in their cancer care experience. The study included participants who self-identified as racially/ethnically diverse and/or 2SLGBTQIA + , diagnosed with cancer between ages 15 and 39 years, currently aged 18 years or older, and received or were receiving cancer care in Canada. Patient partners with lived experience of cancer were recruited as collaborators. Semi-structured virtual interviews were conducted using an interview guide, and transcripts were analyzed using framework analysis. Twenty-three participants (17 racially/ethnically diverse; 1 sexual/gender diverse; 5 both racially and sexually diverse) were interviewed. Positive experiences reported by participants included being able to identify with healthcare providers (HCPs), effective communication, comprehensive information sharing, and access to support services tailored for younger patients. Negative experiences were characterized by perceptions of judgmental attitudes and racialization from HCPs, the necessity of self-advocacy to obtain resources, systemic barriers to care, and psychosocial difficulties. Participants' recommendations for improving cancer care included increasing the diversity of HCPs, implementing equity, diversity, and inclusion training, and enhancing both communication and information dissemination practices. The experiences of diverse AYAs revealed both facilitators and barriers to equitable cancer care. Findings emphasize the need for workforce diversity and equity-informed practices to advance culturally responsive oncology care. Précis: This study examined the cancer care experiences of racially/ethnically diverse and/or 2SLGBTQIA + adolescents and young adults in Canada, revealing both supportive interactions and significant barriers such as discrimination and systemic inequities. Participants recommended increasing provider diversity, equity-focused training, and improved communication to create more inclusive and responsive cancer care.
Body mass index (BMI) is used to identify high-risk groups in childhood and to target early interventions to prevent later metabolic disorders. This is a priority area for research among children born very preterm (VPT) given growing concern with their long-term risks of adverse metabolic outcomes. Two principal international BMI classifications exist for underweight, overweight and obesity (OWOB) in children (International Obesity Task Force (IOTF) and World Health Organization (WHO)), but how the choice of reference affects results of research in children born VPT is unknown. Our objective was to compare the prevalence and risk factors for underweight and OWOB using these two references among five-year-old children born VPT. Data comes from a population-based cohort of children born VPT in 11 European countries in 2011-12 with information from medical records during the neonatal hospitalization and parental questionnaires at age five. BMI at five years of age was classified into underweight and OWOB using IOTF and WHO references (n = 2654 children). Conversion algorithms were also applied to prevalence estimates. Associations with sociodemographic, perinatal and neonatal characteristics were assessed using multinomial logistic regression with multiple imputation and inverse probability weighting to account for missing data and attrition. After applying a cutoff of -1SD to define mild underweight for WHO - since this category exists only for IOTF - the estimated prevalence of total underweight was similar between IOTF and WHO references (27.8% vs 27.0%, respectively). IOTF classified a higher proportion of children as having severe underweight (4.1% vs 1.6%). For OWOB, prevalence estimates were lower using IOTF, particularly among boys (8.6% vs 14.1%). The algorithms provided good conversion (1-2% absolute difference) of prevalence between references for underweight and obesity overall, and overweight for girls, but had a larger error for overweight in boys. Risk factors were similar for underweight and OWOB for both references, with the exception of sex and maternal country of birth. Notably, the IOTF reference identified a lower risk of OWOB among boys, a result not found using WHO references. Clinicians and researchers should be aware of the difference in prevalence of suboptimal BMI when interpreting findings from studies using different classifications and IOTF should be used with caution for investigating sex differences. Given the high prevalence of mild underweight in children born VPT, the cutoff of -1SD should be used with the WHO references in studies of BMI in this population.
Breastfeeding is widely acknowledged as the optimal feeding method for neonatal health. Remote breastfeeding guidance (e.g., using the telephone, text messages, mobile applications, and so on) may improve breastfeeding rates and neonatal outcomes, but its short-term impact and effect across economic regions remain unclear. This systematic review and meta-analysis aimed to assess the effect of remote breastfeeding guidance on neonatal feeding practices and breastfeeding rates. Databases including PubMed, Embase, and the Cochrane Library were screened from inception to November 2024 to identify randomized controlled trials (RCTs) that assessed the effects of remote breastfeeding guidance on breastfeeding rates and neonatal health. Time subgroup analyses evaluated exclusive and any breastfeeding at 3 and 6 months postpartum, together with the effects in developed and less developed regions. Trial Sequential Analysis (TSA) and sensitivity analysis were employed to address heterogeneity and evaluate the robustness of the findings. Thirty RCTs involving 8,389 infants were incorporated into this systematic review and meta-analysis. Compared to the control group, remote breastfeeding support significantly increased the prevalence of exclusive breastfeeding at 3 and 6 months (RR = 1.17, 95% CI 1.11-1.23, P < 0.0001; RR = 1.57, 95% CI 1.38-1.77, P < 0.0001), with modest effects on any breastfeeding (RR = 1.07, 95% CI 1.02-1.13, P = 0.007; RR = 1.05, 95% CI 0.99-1.11, P = 0.11). Infant weight was significantly higher in the intervention groups at 3 and 6 months (MD = 334.39, 95% CI 310.93-357.85, P < 0.00001), representing clinically meaningful gains. A subgroup analysis demonstrated that exclusive breastfeeding provided greater benefits in less developed regions (RR = 1.28, 95% CI 1.23-1.34, P < 0.00001) than in developed regions (RR = 1.12, 95% CI 1.05-1.19, P < 0.00001). TSA and sensitivity analyses confirmed the robustness of the results. Remote breastfeeding guidance plays an important role in increasing breastfeeding rates and promoting physical development, with particularly pronounced effects in less developed regions.
The effects of contact precautions (ie, gowns and gloves) for individual patients colonized with gram-negative (GN) drug-resistant bacteria on sepsis risk in neonates requiring intensive care remain to be clarified. To evaluate the noninferiority of standard hand hygiene disinfection vs standard hygiene disinfection plus extended barrier precautions for infants colonized with third-generation cephalosporins-resistant GN bacteria (3GCR-GNB). This cluster-randomized clinical trial was conducted from 2020 to 2023 in 12 German tertiary care neonatal intensive units caring for neonates with high risk for infections with GNB for 24 months, with crossover after 12 months. Follow-up and data curation were completed December 31, 2024, and statistical analysis was finalized on July 31, 2025. The intervention was standard hand hygiene disinfection compared with current recommendations, ie, hygiene disinfection plus extended barrier precautions with gowns and gloves for routine care of infants colonized with 3GCR-GNB. The primary outcome was the rate of health care-associated GNB bloodstream infections (BSI) at infant level in all neonates requiring intensive care in the cluster, assuming 5% as noninferiority margin delta; secondary outcomes included transmission rates of 3GCR-GNB and rates of any infection. The primary analysis was based on an overall sample size of 12 sites with crossover at 12 months, making 24 clusters with 9731 neonates. During the standard hand hygiene disinfection periods, 22 of 4699 infants (0.5%) developed GNB BSIs at infant level, compared with 25 of 5032 infants (0.5%) cared for during the extended barrier precaution periods (risk difference [RD], -0.03%; 95% CI, -0.43% to 0.38%; noninferiority P < .001). At least 1 nosocomial transmission with 3GCR-GNB was noted during 41 of 144 months in the intervention period and 54 of 144 months in the control period (RD, -9.03%; 95% CI, -27.79% to 9.74%), with involvement of 116 patients (2.5%) vs 149 patients (3.0%) (RD, -0.44%, 95% CI, -2.47% to 1.58%). The total rate of BSI was 2.1% in neonates during the intervention period vs 2.0% during the control period (RD, 0.12%; 95% CI, -1.39% to 1.64%). In this cluster-randomized clinical trial, standard hand hygiene disinfection for the care of infants colonized with 3GC-GNB was noninferior to standard hygiene disinfection plus extended barrier precautions. German Clinical Trials Register identifier: DRKS00019103.
Enzymatic modification of gliadin peptides by calcium-dependent transglutaminase 2 (TG2) plays a central role in the pathogenesis of celiac disease (CD) and is considered a potential therapeutic target. Recently, anthocyanins (ACN) such as cyanidin-3-glucoside (C3G) and delphinidin-3-glucoside (D3G) have gained attention in CD research for their anti-inflammatory, antioxidant and gliadin-binding properties. This study examined whether C3G and D3G modulate TG2 activity and cytokine-induced inflammation in human intestinal cells. TG2 activity was analyzed using gliadin substrates and TG2 expression was assessed after IFN-γ and TNF-α stimulation. Cell viability after ACN, IFN-γ and TNF-α incubation was tested with a resazurin-based fluorometric assay. Docking and STD-NMR experiments were conducted to explore the molecular interactions involved. D3G significantly reduced TG2-mediated crosslinking of gliadin and C3G of 5-biotinamidopentylamine as a synthetic substrate of TG2. STD-NMR and in silico docking experiments revealed a molecular interaction of ACN with calcium binding sites of TG2 which are essential for its enzymatic function. In addition, C3G and D3G improved cell viability under IFN-γ and TNF-α exposure and D3G reduced upregulation of TG2 mRNA under IFN-γ stimulation. Here, in silico docking experiments suggested that both ACN may interact with the assembly of cytokines and their corresponding cellular receptors. In conclusion, our data indicates that C3G and D3G reduce TG2-activity and mitigate cytokine-mediated inflammatory effects by a direct molecular interaction. This supports their potential as natural modulators of TG2 in the context of CD.
The transition of care from paediatric to adult healthcare services is a vulnerable period for patients with inborn errors of immunity (IEI), a heterogeneous group of primary immunodeficiency disorders characterized by chronic immune dysfunction and significant morbidity. With advances in diagnosis and treatment, an increasing number of patients with IEI are now reaching adulthood, making the management of this transition a growing clinical priority. Inadequate transition is associated with medical complications, treatment non-adherence, discontinuity of care, increased healthcare utilization, and poorer long-term outcomes. Despite growing awareness, condition-specific and standardized transition guidelines for IEI remain largely absent, leaving clinicians without a clear framework to guide this critical phase. In this context, the present review proposes a structured, multidisciplinary transition protocol designed specifically for paediatric patients with IEI to support therapeutic adherence, continuity of care, and patient well-being. This practice-informed narrative review integrates a non-systematic appraisal of the available literature, expert clinical consensus, and the practical experience of a dedicated Italian centre. Central to this model are the early identification of patients eligible for transition, beginning around age 14, and the gradual involvement of a multidisciplinary team, with shared responsibility between paediatric and adult specialists throughout an overlap period of at least three years. Clear documentation, including a standardized clinical dossier and final transition report, along with measurable process and outcome indicators such as infection rates, follow-up adherence, and patient-reported quality of life, ensures continuity of care and ongoing support. The framework also addresses immunoglobulin replacement therapy options, including intravenous, subcutaneous, and facilitated subcutaneous immunoglobulin, which each offer distinct advantages depending on patient needs and life stage. Patient and caregiver empowerment, timely management of comorbidities, and regular reassessment of individual needs are core components. Although resource-intensive, the proposed model is designed to be adaptable to different healthcare settings. Limitations, including reliance on multidisciplinary resources and the absence of prospective validation, are acknowledged, and future research to evaluate its impact on clinical outcomes is warranted. Through coordinated, standardized strategies, this work aims to bridge the gap between paediatric and adult healthcare, reducing care discontinuity and supporting successful long-term disease management in adulthood.
Cardiac surgery with cardiopulmonary bypass (CPB) in young children is associated with systemic stress, gastrointestinal dysfunction, and impaired nutritional recovery. The role of gut microbiome disruption and short-chain fatty acid (SCFA) metabolism in these processes remains insufficiently studied. To evaluate changes in gut microbiome composition, SCFA profiles, and nutritional status in children aged 0-3 years after CPB, and to assess their association with postoperative feeding intolerance and impaired growth. This prospective observational study included 20 children undergoing cardiac surgery with CPB. Stool samples were collected preoperatively and during the early postoperative period. Microbiota composition was assessed using culture-based microbiological methods, and fecal SCFA concentrations were measured by gas chromatography. Clinical, anthropometric, and laboratory parameters were assessed, and their associations with CPB characteristics and microbiome alterations were analyzed. The postoperative period was characterized by significant intestinal dysbiosis, including reduced abundance of beneficial bacteria (Bifidobacterium, Lactobacillus, Bacteroides) and decreased SCFA-producing taxa. Fecal butyrate and propionate levels were significantly reduced. These changes were associated with increased intestinal inflammation, feeding intolerance, impaired nutrient absorption, and insufficient weight gain. The severity of dysbiosis correlated with CPB duration. CPB in early childhood is associated with disruption of gut microbiota and reduced SCFA production, which are linked to postoperative feeding intolerance and impaired nutritional recovery. Targeted monitoring and modulation of the gut microbiome may improve clinical outcomes in pediatric cardiac surgery patients.
The aim of this study is to synthesize and evaluate the effectiveness of interventions aimed at improving endotracheal intubation success in neonates and infants. PubMed, Scopus, and Web of Science were searched from inception through July 2025. Randomized studies involving neonatal or infant endotracheal intubation were included regardless of intervention or comparator. Two reviewers independently extracted data and assessed risk of bias. Data were pooled using a random-effects inverse-variance model. Results are reported as risk ratios (RRs) with 95% confidence intervals (CIs). Certainty of evidence was assessed using the GRADE approach. Thirty studies published between 2002 and 2025 were included from 287 screened records. Most intubations were elective and performed in neonatal intensive care units or operating rooms. Video laryngoscopy improved first-attempt success compared with direct laryngoscopy (RR 1.13; 95% CI 1.06-1.20; high-certainty evidence). Pharmacologic interventions, particularly neuromuscular blocking agents and sedatives, generally increased success. Noninvasive respiratory support during intubation improved success (RR 1.18; 95% CI 1.02-1.38; moderate-certainty evidence). Time to successful intubation was similar across most interventions, except for neuromuscular blockade, which shortened intubation duration. Desaturation-related outcomes did not differ.  Video laryngoscopy improves first-attempt intubation success with high-certainty evidence, and noninvasive respiratory support most likely improves success. These findings support their use during neonatal and infant intubation. • Intubation in neonates and infants carries a high complication risk, making fi rst-attempt successcritical. • Video laryngoscopy and pharmacological premedication each improve intubation conditions but have previouslybeen evaluated in isolation. • Pooled randomized evidence confi rms with high certainty that video laryngoscopy improves fi rst-attempt success over direct laryngoscopy without prolonging intubation time. • Non-invasive respiratory support during intubation most likely improves fi rst-attempt success and physiologicalsafety.
Treatment strategies in patent ductus arteriosus (PDA) in preterm infants (PIs) have evolved in recent years and vary substantially between centers. While recent recommendations increasingly advocate for a more conservative approach to PDA management, transcatheter PDA closure (TCPC) has simultaneously become a well-established alternative to surgical ligation-even in very small PIs-after failure of medical treatment. Particularly in light of the ongoing conflicting perspectives in the field of optimal PDA management in PIs, our objective was to compare frequency, efficiency, and complications of surgical closure versus TCPC in a real-world setting. Between 2022 and 2023, we conducted a prospective nationwide hospital-based surveillance study including preterm infants < 32 weeks gestation and < 1500 g birthweight who underwent either surgical or transcatheter PDA closure. Standardized data on PDA treatment strategies, including medical therapy and complications, were collected by the German Paediatric Surveillance Unit (GPSU) and outcomes evaluated using the Desirability of Outcome Ranking (DOOR) method. Data from 110 infants were analyzed. Ninety-three percent (102/110) received at least one kind of medical treatment before definite mechanical closure with ibuprofen most widely used followed by paracetamol. Surgical closure was performed in 70 infants and transcatheter closure in 40 infants. Infants in the surgical group were more immature at birth (24 + 3 weeks [IQR 23 + 5-25 + 3] vs. 25 + 3 weeks [IQR 24 + 3-27 + 0], p  0.001), had lower birthweight (635 g vs. 733 g, p 0.009), and had lower weight at the time of surgery compared to catheterization (915 g vs. 1200 g, p < 0.001). Complications were reported in 15% (10/68) after surgical closure and in 26% (10/39) after TCPC but did not differ in the DOOR analysis.  In this nationwide study from Germany, transcatheter PDA closure was performed in approximately one-third of preterm infants, whereas surgical closure remained the predominant approach, particularly in smaller and more immature infants. The high incidence of adverse events following both methods-TCPC and surgical closure-warrants close ongoing surveillance. Substantial off-label use of paracetamol reflects evolving medical practice. • PDA in PIs remains a common clinical challenge, with a wide range of treatment strategies across NICUs. • New transcatheter PDA closure (TCPC) devices have recently been approved for use in preterm infants weighing > 700 g, expanding interventional options in this vulnerable population. • Surgical PDA closure seems to be still the preferred PDA treatment option in Germany especially in more immature infants. • Overall safety demonstrated no meaningful difference between TCPC and surgical PDA closure.
Preterm and low-birthweight infants are at risk of anemia due to a variety of factors, including low levels of erythropoietin. They may therefore benefit from erythropoiesis-stimulating agents (ESAs). However, controversy remains about their effectiveness and safety, not only in reducing blood transfusions but also in improving clinical outcomes. To assess the benefits and harms of early administration of ESAs in preterm or low-birthweight infants. We searched CENTRAL, MEDLINE, Embase, Scopus, DOAJ, and trial registries to 31 March 2025, and checked the reference lists of studies and systematic reviews for potentially relevant studies. Randomized controlled trials (RCTs) comparing early (initiated before eight days of life) ESAs (erythropoietin or darbepoetin) to placebo or no intervention among preterm (< 37 weeks' gestation) or low-birthweight (< 2500 g) infants. Outcomes included mortality during initial hospital stay (all-cause mortality), moderate to severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age, proportion of infants exposed to one or more red blood cell (RBC) transfusions, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and severe intraventricular hemorrhage (sIVH). We used the Cochrane RoB 1 tool to assess risk of bias. We performed data collection and analyses according to the methods of Cochrane Neonatal (fixed-effect meta-analysis using the inverse-variance method). We analyzed categorical data using risk ratio (RR) and continuous data using mean difference (MD), and reported the 95% confidence interval (CI) on all estimates. We used GRADE to assess the certainty of evidence. We included 37 studies (n = 6724), five (n = 3052) of which are new. Two studies (n = 752) investigated darbepoetin, and 35 studies (n = 5972) investigated erythropoietin. ESAs compared to placebo or no intervention Mortality: ESAs probably result in little to no difference in mortality during initial hospital stay (RR 0.93, 95% CI 0.80 to 1.09; I² = 0%; 24 studies, 5217 participants; moderate-certainty evidence). Subgroup analysis suggests that early use of erythropoietin probably results in little to no difference in mortality (RR 0.91, 95% CI 0.77 to 1.09; I² = 0%; 23 studies, 4505 participants), and early use of darbepoetin probably results in little to no difference in mortality (RR 1.00, 95% CI 0.71 to 1.43; I² = 0%; 2 studies, 712 participants). NDI: ESAs may reduce moderate to severe NDI at 18 to 26 months' corrected age (RR 0.81, 95% CI 0.68 to 0.95; I² = 86%; 3 studies, 1707 participants; low-certainty evidence). Subgroup analysis suggests that early use of erythropoietin may reduce moderate to severe NDI at 18 to 26 months' corrected age (RR 0.79, 95% CI 0.66 to 0.95; I² = 93%; 2 studies, 1239 participants), while early use of darbepoetin may result in little to no difference in moderate to severe NDI at 18 to 26 months' corrected age (RR 0.87, 95% CI 0.59 to 1.28; I² not applicable; 1 study, 468 participants). Transfusions: ESAs may reduce the proportion of infants exposed to one or more RBC transfusions (RR 0.79, 95% CI 0.76 to 0.83; I² = 56%; 21 studies, 3507 participants; low-certainty evidence). Subgroup analysis suggests that erythropoietin may reduce the proportion of infants exposed to one or more RBC transfusions (RR 0.80, 95% CI 0.76 to 0.84; I² = 56%; 20 studies, 2795 participants); darbepoetin may reduce the proportion of infants exposed to one or more RBC transfusions (RR 0.75, 95% CI 0.68 to 0.84; I² = 0%; 2 studies, 712 participants). ROP (any stage): ESAs result in little to no difference in incidence of ROP (RR 0.91, 95% CI 0.83 to 1.00; I² = 0%; 14 studies, 3844 participants; high-certainty evidence). Subgroup analysis suggests the use of either erythropoietin (RR 0.92, 95% CI 0.84 to 1.02; I² = 0%; 13 studies, 3230 participants) or darbepoetin (RR 0.83, 95% CI 0.58 to 1.17; I² = 0%; 2 studies, 614 participants) results in little to no difference in incidence of ROP. NEC (any stage): ESAs probably reduce the incidence of NEC (RR 0.74, 95% CI 0.62 to 0.87; I² = 0%; 20 studies, 5749 participants; moderate-certainty evidence). Subgroup analysis suggests that early use of erythropoietin probably reduces the incidence of NEC (RR 0.72, 95% CI 0.61 to 0.85; I² = 0%; 19 studies, 5041 participants), while early use of darbepoetin probably results in little to no difference in incidence of NEC (RR 1.08, 95% CI 0.54 to 2.15; I² = 0%; 2 studies, 708 participants). sIVH (grade ≥ 3): ESAs probably reduce the incidence of sIVH (RR 0.70, 95% CI 0.56 to 0.89; I² = 43%; 9 studies, 2458 participants; moderate-certainty evidence). Subgroup analysis suggests that early use of erythropoietin probably reduces the incidence of sIVH (RR 0.72, 95% CI 0.57 to 0.91; I² = 47%; 9 studies, 2396 participants), while early use of darbepoetin probably results in little to no difference in incidence of sIVH (RR 0.40, 95% CI 0.11 to 1.41; I² not applicable; 1 study, 62 participants). Of note, the test for subgroup differences between erythropoietin and darbepoetin revealed no evidence of a difference for the outcomes of mortality, moderate to severe NDI, NEC, sIVH, ROP, and the proportion of infants exposed to RBC transfusion. We downgraded the certainty of evidence for inconsistency, imprecision, and high risk of bias in the included studies. Early use of ESAs probably results in little to no difference in mortality (moderate-certainty evidence); may reduce moderate to severe NDI at 18 to 26 months' corrected age (low-certainty evidence); has little to no effect on ROP (high-certainty evidence); may reduce the proportion of infants exposed to one or more RBC transfusions (low-certainty evidence); and probably reduces both NEC and sIVH (moderate-certainty evidence). Given the benefits of ESAs, future research should focus on cost-effectiveness, equity, feasibility of implementation, and acceptability to different stakeholders of the routine use of erythropoietin or darbepoetin among preterm or low-birthweight infants. No funding was received for this review. Protocol (and previous versions) available via 10.1002/14651858.CD004863; 10.1002/14651858.CD004863.pub2; 10.1002/14651858.CD004863.pub3; 10.1002/14651858.CD004863.pub4; 10.1002/14651858.cd004863.pub5; 10.1002/14651858.CD004863.pub6.
Glycogen storage disease type IX (GSD IX) is an inherited metabolic disorder characterized by marked clinical heterogeneity and variable severity. Dietary therapy is considered the cornerstone of management, but evidence on treatment strategies, efficacy, and safety remains limited. This study aimed to systematically synthesize available data on therapeutic approaches and clinical outcomes in GSD IX. A focused analysis of treatment-related data was conducted from a previously performed PRISMA-based systematic review. Clinical studies reporting treatment and follow-up data in genetically confirmed GSD IX patients were included. Among 400 patients identified in the original review, 129 from 26 studies had treatment and follow-up data available. Dietary management combined with uncooked cornstarch (UCCS) was the most common approach (96.1%), with highly heterogeneous protocols. Hepatic manifestations improved in 59/129 (45.7%) of patients, and hypoglycemia in 45/129 (34.9%). Growth outcomes were variable, with catch-up growth in 14.0% and persistent impairment in 19.4%, although data were often missing. Muscle involvement was rarely assessed. No treatment-related adverse events were reported. However, disease-related complications were described, including liver cirrhosis, neurological involvement, osteopenia/osteoporosis, and two deaths in GSD IXa patients. Dietary therapy combined with UCCS remains the mainstay of treatment in GSD IX and is associated with improvement in key clinical domains. However, evidence is limited, heterogeneous, and largely based on small studies. Data on modified cornstarch formulations, such as Glycosade®, are scarce. Prospective studies and standardized treatment protocols are needed to support evidence-based management.
Improving Continuous kidney replacement therapy (CKRT) Outcomes in Neonates and Infants Through Interdis ciplinary Collaboration (ICONIIC) is a multicenter quality improvement and research registry. We aimed to identify programmatic structures and educational practices for neonatal and infant CKRT. A survey focusing on care delivery and models, units offering therapy, staff-to-patient ratios, and education protocols was distributed to institutions in ICONIIC using the Carpediem machine. Of the 13 responding sites, 11 used the Carpediem machine in Pediatric Intensive Care Units (ICUs), 9 in Neonatal ICUs, and 8 in Cardiac ICUs. A collaborative care model was most common (69.2%). While education practices varied, all sites required nurse-specific training, and all but one mandated provider oversight during CKRT initiation. Understanding these practices may inform best practices for neonatal and infant CKRT.
To evaluate the analgesic efficacy and physiological effects of oral sucrose during lumbar puncture (LP) in term neonates. This double-blind, randomised trial enrolled 60 full-term neonates undergoing LP. Participants were randomly given 2 mL of 25% oral sucrose or sterile water 2 min before the procedure. The primary outcome was pain score change from baseline via the Neonatal Infant Pain Scale (NIPS). Secondary outcomes included changes in heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO₂). Measurements were taken at baseline, 1 min, and 3 min post-LP. The sucrose group showed significantly smaller changes in NIPS scores at 1 min (1.0 vs 5.0, p<0.001) and 3 min (0.0 vs 4.0, p<0.001), along with smaller HR increases (p=0.012) and SpO₂ decreases (p=0.023) at 1 min post-procedure. Clinically significant tachycardia (HR >160 bpm) occurred in 40% of controls vs 13.3% of sucrose-treated infants (p=0.045), and desaturation (SpO₂ <90%) in 26.7% of controls vs 6.7% of the sucrose group (p=0.038). A 2 mL dose of 25% oral sucrose administered 2 min prior to LP is a safe and effective intervention that significantly reduces behavioural and physiological markers of pain in term neonates during the immediate post-procedural period.
Prostaglandin E-major urinary metabolite (PGE-MUM) is a stable urinary marker of prostaglandin E2 metabolism and it is used for monitoring inflammation. However, its physiological dynamics in neonates across gestational ages remain unclear. Here, we aimed to investigate the longitudinal changes in PGE-MUM levels during the first 14 postnatal days (PND) in neonates with varying gestational age at birth (GA) and to examine its association with GA and neonatal inflammatory conditions. This prospective observational study enrolled 40 neonates admitted to the neonatal intensive and growing care units at the University of Tokyo Hospital. Urinary PGE-MUM, measured by chemiluminescent enzyme immunoassay and corrected for creatinine, was tracked across PND0-14. Data from 40 neonates (median GA: 36.3 weeks) were analyzed. Urinary PGE-MUM levels were significantly higher than adult reference values and exhibited diverse temporal patterns. Very preterm infants (<32 weeks GA) demonstrated persistently high levels or increasing trends, while term infants (≥37 weeks GA) showed gradual declines. A significant negative correlation was observed between GA and PGE-MUM at PND2 onward. Neonates with allied disorders of Hirschsprung's disease exhibited markedly elevated PGE-MUM levels at birth, followed by a sharp decline after surgical intervention. Those with non-IgE-mediated gastrointestinal food allergy displayed relatively low initial levels, gradually decreasing over time. Urinary PGE-MUM levels were significantly elevated in neonates compared to adults, with a strong negative correlation with GA. These findings suggest their potential as a biomarker for neonatal gastrointestinal and pulmonary diseases. Further multicenter studies are warranted to validate clinical utility.
The aim of this study is to evaluate the performance of PRISM III and pediatric early warning score (PEWS) for predicting increased level of care in an intermediate care unit (IMCU) and to describe the factors associated with it. This was a retrospective observational study in an IMCU of a tertiary university hospital without an on-site pediatric intensive care unit (PICU). Patients younger than 14 years old admitted to IMCU (June 2021 to September 2024) were included. Area under the curve (AUC) for "increased level of care"-composite outcome including high respiratory support, invasive procedures, prolonged length of stay, or PICU-transfer-was calculated for both scores. Of 567 patients included (median age 15 months [IQR 3-49]; 57.8% male), 269 (47.4%) needed increased level of care. AUC of PRISM III was 0.545 (CI95% 0.497-0.592), whereas AUC of PEWS was 0.697 (CI95% 0.654-0.740); sensitivity was 43.5% (CI95% 37.8-49.3) and specificity was 86.6% (CI95% 82.3-90.1). Results were consistent in sensitivity analyses. Healthcare workers or family concern was associated with increased level of care [aOR 4.127 (CI95% 2.492-6.835)] and PICU-transfer [aOR 8.180 (CI95% 2.920-22.912)].  Neither PRISM III nor PEWS was accurate to predict increased level of care in IMCU. Healthcare worker or family concern was associated with both increased level of care and PICU-transfer. These findings highlight the need for IMCU-specific severity tools and the importance of individual assessment. • Early warning scores (PEWS) and PRISM III are widely used in general wards and PICU, respectively. • However, their performance in intermediate care units (IMCU) remains poorly defined. • Both PRISM III and PEWS have limited accuracy in predicting the need for increased level of care within an IMCU. • The subjective concern of staff or family members was associated with clinical worsening and PICU-transfer.
Given the increasing prevalence of neurodevelopmental disorders, this study examined the association between autism and neurodevelopmental delays and exposure to intrapartum labor epidural analgesia (LEA) and synthetic oxytocin (OT) in offspring. The data were obtained from various questionnaires, including the Japanese Ages and Stages Questionnaires, Third Edition. Using data from a large-scale longitudinal birth cohort study in Japan, 72,801 participants were enrolled and follow-up to age 4 years. Exposure during labor was categorized into four groups: no-exposure, OT, LEA, and LEA-OT. Adjusted odds ratios for autism were 2.35 (95% CI 1.44-3.83) in the LEA-OT group and 2.41 (95% CI 1.31-4.45) in the LEA group. The E-values for the point estimates were 4.16 in the LEA-OT group and 4.29 in the LEA group, and those for the lower limits of the 95% confidence intervals were 2.39 and 2.05, respectively, indicating only moderate robustness to unmeasured confounding. Associations with autism were consistent across analyses in the LEA-OT group, but in sex-stratified analyses, only males showed an association. No consistent associations with neurodevelopmental delays were observed in any exposure groups. Since residual confounding cannot be excluded, with limited external validity, these findings warrant replication in independent cohorts to clarify causality.