Search Results (1,482)

Background: Preterm premature rupture of membranes (PPROM) before 32 weeks of gestation with prolonged latency is associated with substantial neonatal morbidity, including Dry Lung Syndrome (DLS), pulmonary hypoplasia (PH), bronchopulmonary dysplasia (BPD), and death. Accurate individualized risk stratification remains elusive, as the interacting contributions of amniotic fluid dynamics, inflammatory status, and microbiological burden are inadequately captured by traditional statistical approaches. Methods: We performed a retrospective, exploratory–predictive analysis of 66 pregnancies complicated by second-trimester PPROM with latency exceeding 14 days. Elastic Net and Random Forest models were trained across six clinically defined predictor domains using a multi-stage block modelling strategy. To address the clinically relevant distinction between antenatal and postnatal information, results are reported separately for Model A—comprising exclusively antenatal predictors available during expectant management (gestational age at PPROM, latency, amniotic fluid trajectory, inflammatory status, vaginal microbiome at admission)—and Model B, which additionally incorporates postnatal variables and characterizes the full mechanistic perinatal risk trajectory. Binary and ordinal outcomes included DLS, PH, BPD, intraventricular hemorrhage (IVH), and neonatal death. Pairwise interaction models were additionally computed to identify cross-domain risk constellations. Results: Distinct predictor architectures emerged per outcome. Pulmonary hypoplasia was most strongly associated with temporal features of oligohydramnios—particularly the persistence and timing of SDP < 1 cm—rather than isolated measurements. For DLS, the antenatal model (Model A) achieved AUC 0.776, driven by gestational maturity and inflammatory status; surfactant administration—a postnatal variable reflecting therapeutic response rather than an antenatal risk factor—dominated only the mechanistic Model B. Neonatal death was driven by a combined profile of respiratory support burden, amniotic fluid persistence, and co-morbidity. IVH showed consistently high ordinal predictability (accuracy 0.863), with amniotic fluid dynamics and microbiological burden as leading contributors. BPD remained the least linearly separable endpoint across all configurations. Conclusions: Multi-domain machine learning reveals outcome-specific, cross-domain risk architectures following second-trimester PPROM that are invisible to conventional statistical models. Longitudinal amniotic fluid trajectory is the dominant antenatal determinant of structural pulmonary morbidity, while microbiological burden independently shapes neurological risk. These findings support prospective validation of integrated ML-based risk stratification tools for individualized antenatal counselling in this high-risk population. Full article

Background: Respiratory diseases (RDs), including asthma, COVID-19, chronic obstructive pulmonary disease (COPD), and pneumonia, remain a major global health challenge, contributing substantially to global morbidity and mortality. Conventional diagnosis relies heavily on clinicians’ expertise to interpret respiratory sounds and radiographic images, a process that can be subjective, time-consuming, and prone to inter-observer variability. Recent advances in artificial intelligence (AI) and machine learning (ML) have enabled automated diagnostic approaches that can improve the efficiency, consistency, and scalability of respiratory disease detection. However, existing research remains fragmented across different data modalities. Methods: This review systematically analyzes recent studies on AI-based respiratory disease detection using both visual modalities (e.g., chest X-rays, computed tomography (CT) scans, and ultrasound) and audio modalities (e.g., cough and breath sounds). To provide a comprehensive perspective, the reviewed literature is organized using a unified taxonomy that categorizes existing approaches into three main groups: audio-based, visual-based, and audio–visual-based methods. In addition, two conceptual frameworks are proposed to illustrate representative pipelines for audio-based and visual-based respiratory disease classification. Results: The analysis reveals that most existing studies focus on single-modality approaches, while multimodal integration remains relatively underexplored. Only a limited number of studies combine audio and visual data within unified frameworks, primarily due to the scarcity of synchronized multimodal datasets collected from the same patients. The proposed taxonomy and conceptual frameworks provide a structured basis for comparing existing methods, identifying methodological trends, and highlighting key research gaps in multimodal respiratory disease detection. Conclusions: Future research should prioritize the development of multimodal datasets, robust evaluation protocols, and interpretable and lightweight AI models suitable for real-world clinical deployment. Advancing multimodal integration has the potential to significantly enhance the accuracy, reliability, and clinical applicability of AI-driven respiratory disease diagnosis systems. Full article

The aim of this study was to determine the effects of PM10 and PM2.5 particulate matter pollution from the coal mining sector in the three municipalities of Cesar, La Guajira, and El Magdalena on respiratory morbidity in children under 5 years of age and adults over 60 years of age residing in these municipalities. This descriptive time series study included three municipalities in three departments: Algarrobo, Albania, and La Jagua de Ibirico. The SEVCA (Seasonal Environmental Monitoring System) was used to collect PM10 and PM2.5 pollutants. Data on secondary source air quality (RIPS) were collected from the public health services (ESE) in each municipality. The daily average concentration of μg/m³ was used for the statistical analysis of the pollutants. A time series statistical model was applied to compare the temporal variations in exposure levels and the event itself. The air quality data databases were analyzed using descriptive statistics. A logistic regression model was used to assess the association between pollutants and air quality. To account for the effects of time lags in air quality data, moving averages with lags of 0 to 3 days were used. Statistical analyses were performed using R version 4.5.1. We found daily averages of ARI in children under 5 years of age and adults over 60 years of age in the three municipalities of (1.35) admissions per day. The average daily concentrations of μg/m3 for Algarrobo were (29.79 μg/m³) for PM10 and (12.68 μg/m³) for PM2.5, for Albania (33.49 μg/m³) for PM10 and (13.23 μg/m³) for PM2.5, and for La Jagua (41.42 μg/m³) for PM10 and (15.18 μg/m³) for PM2.5. Significant positive associations greater than 1 were obtained between ARI admissions and PM10 and PM2.5 pollutants, with an RR of 1.105, 1.106, 1.125, 1.124, 1.157, and 1.155 95% CI, when PM10 and PM2.5 increase by 10 μg/m³ and for delays of 1 and 1–3 days. In conclusion, we observed significant positive associations between hospital admissions for ARI in children under 5 years of age and adults over 60 years of age for the three municipalities and the pollutants PM10 and PM2.5, which leads us to conclude that there is an epidemiological association and that the change in μg/m³ levels represents a change in the risk of hospital admission for ARI for children under 5 years of age and older adults in this coal corridor of the Colombian Caribbean. Full article

Background and Objectives: Postoperative pulmonary complications (PPCs) remain an important cause of morbidity after cardiac surgery. Driving pressure (DP), defined as the difference between plateau pressure and positive end-expiratory pressure, has been proposed as a bedside marker of respiratory system mechanics during lung-protective ventilation. However, its relationship with PPCs in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) remains uncertain. This study aimed to evaluate the association between intraoperative DP and PPCs following CPB-supported cardiac surgery. Materials and Methods: This single-center prospective observational study included 99 adult patients undergoing elective cardiac surgery with CPB. All patients were ventilated using a standardized lung-protective strategy with a tidal volume of 6 mL/kg predicted body weight and a fixed PEEP of 5 cmH₂O. Patients were categorized according to intraoperative DP as Group I (DP < 13 cmH₂O, n = 66) and Group II (DP ≥ 13 cmH₂O, n = 33). The primary outcome was a composite PPC endpoint, defined as the occurrence of at least one EPCO-defined pulmonary complication during the postoperative hospital stay. Multivariable logistic regression was performed to assess whether pre-CPB DP was independently associated with PPCs after adjustment for body mass index, CPB time, and age. Results: Patients with DP ≥13 cmH₂O had higher post-CPB and ICU-admission lactate concentrations. Pneumothorax, pleural effusion, atelectasis, CPAP requirement, and prolonged mechanical ventilation were more frequent in the elevated-DP group. Mechanical ventilation duration, ICU stay, and hospital stay were also longer in this group. Composite PPCs occurred in 41 patients (41.4%). Although higher pre-CPB DP showed a non-significant trend toward increased PPC risk in univariable analysis (OR 1.121, 95% CI 0.988–1.273; p = 0.077), it was not independently associated with the composite PPC endpoint after adjustment (adjusted OR 1.091, 95% CI 0.952–1.251; p = 0.212). In contrast, higher pre-CPB DP was significantly associated with prolonged postoperative ventilation and longer mechanical ventilation, ICU, and hospital stay durations. Conclusions: Elevated intraoperative DP was associated with a higher unadjusted burden of PPCs and delayed postoperative recovery after CPB-supported cardiac surgery. However, pre-CPB DP was not an independent predictor of the composite PPC endpoint after adjustment for relevant confounders. These findings suggest that DP may serve as a clinically useful marker of impaired respiratory mechanics and postoperative vulnerability rather than as an independent causal determinant of PPCs. Full article

Background: The increasing incidence and improved survival rates of multiple myeloma (MM) have led to a growing healthcare burden, particularly in terms of hospitalizations. In addition, infection-related complications remain a major cause of morbidity and mortality in these patients. The impact of infection control measures implemented during the COVID-19 pandemic on hospitalization patterns in MM is not well-established. Methods: We conducted a retrospective observational study including all hospital admissions of patients with MM in a tertiary hospital in Spain across three different periods: 2008, 2018, and May 2020 to April 2021 (COVID-19 pandemic period). We analyzed the proportion of admissions, cumulative length of stay, causes of hospitalization, and infection-related complications. Results: The proportion of hospitalizations due to MM increased significantly from 14% in 2008 to 29.8% in 2018 (p < 0.001), along with a parallel increase in cumulative length of stay (14.4% vs. 27.1%, p < 0.001). During the COVID-19 period, a significant reduction in the proportion of admissions was observed compared to 2018 (21.2% vs. 29.8%, p = 0.0029), while cumulative length of stay showed a non-significant decrease. The proportion of infection-related admissions remained stable during the pandemic period, although the absolute number of infections decreased, including respiratory infections. Notably, the incidence of nosocomial pneumonia decreased significantly (26.3% vs. 9.6%, p = 0.028). Conclusions: Compared with 2008, patients with MM accounted for a substantially higher proportion of hospital admissions and cumulative hospital stay in 2018, reflecting the increasing healthcare burden associated with this disease. During the COVID-19 period, a significant reduction in nosocomial pneumonia was observed, suggesting that infection-control strategies may help reduce respiratory complications in patients with MM. Full article

Background: Extremely and very preterm infants are at high risk for adverse neurodevelopmental outcomes. Early prediction remains challenging when relying on static clinical markers or single time-point neuroimaging. Serial cranial ultrasound (CUS) enables repeated bedside assessment of cerebral growth and may provide longitudinal trajectory biomarkers integrable with routine clinical data. Methods: In this retrospective two-center cohort study, 89 preterm infants (<32 weeks’ gestation and/or <1500 g birth weight) were assessed using the Bayley-III at 24 months corrected age. Brain volume trajectory features were derived from serial CUS using a standardized ellipsoid model. A three-level analytical framework was applied as follows: univariate regression (62 models, Bonferroni and Benjamini–Hochberg correction), multivariate SVM classification with five-fold GroupKFold cross-validation, ensuring patient-level data separation and feature importance analysis with interaction characterization using stratified Spearman correlation and two-dimensional partial dependence plots. Results: Multivariate classification yielded modest but above-chance performance (balanced accuracy 0.277–0.463, Cohen’s κ 0.042–0.152). Respiratory morbidity duration—mechanical ventilation and BPD severity—were the most robustly associated univariate predictors, surviving Bonferroni correction. Brain volume trajectory features showed no significant univariate associations but contributed conditionally within the multivariate framework as follows: the interaction between brain volume slope and trajectory linearity was the strongest for cognitive outcome (Δr = 0.47), and postnatal growth restriction showed amplified adverse effects at lower birth weight for motor outcome (Δr = 0.47). Conclusions: This study demonstrates the value of ML methods as structured analytical tools for characterizing predictor–outcome relationships in preterm neurodevelopment; respiratory morbidity and brain volume trajectory features emerged as the most informative predictor classes. Prospective multicenter validation is required before clinical translation. Full article

Ataxia–telangiectasia is a rare, autosomal recessive primary immunodeficiency caused by mutations in the ATM gene on chromosome 11, which encodes a serine–threonine kinase essential for the recognition and repair of DNA double-strand breaks. The disease is characterized by progressive neurological impairment, immunological dysfunction, and an increased susceptibility to recurrent infections and malignancies. Pulmonary involvement represents a major source of morbidity and frequently arises from chronic infections, aspiration, and impaired airway clearance, ultimately leading to the development of bronchiectasis. The case of a 15-year-old adolescent with a history of recurrent aspiration pneumonias, neuropsychomotor developmental delay, and severe malnutrition is reported, who was admitted for evaluation of chronic productive cough, fever, and dysphagia. Comprehensive clinical assessment and ancillary investigations revealed recurrent respiratory infections, gastroesophageal reflux, and typical features of ataxia–telangiectasia, including cerebellar ataxia, oculomotor apraxia, and conjunctival telangiectasias. Additionally, bronchiectasis was identified as a secondary consequence of the underlying neurological and immunological impairment. This case highlights the diagnostic challenges posed by ataxia–telangiectasia in pediatric patients presenting with chronic respiratory symptoms and emphasizes the importance of early recognition of the underlying systemic disorder. A multidisciplinary approach is essential for accurate diagnosis and optimized management, aiming to address both the primary disease and its pulmonary complications. Full article

Sierra Leone faces persistently high neonatal and maternal mortality rates, driven largely by delayed recognition and treatment of newborn respiratory distress and postpartum hemorrhage. In this protocol, we describe the planned implementation of a bundle of maternal and newborn clinical practices over a 36-month period across nine public health facilities in the Greater Freetown area and Bo District to address these critical gaps. The service delivery improvements include the World Health Organization (WHO) Essential Newborn Care Course (ENCC) Parts 1 and 2; Vayu bubble continuous positive airway pressure (bCPAP) and oxygen blenders for respiratory support; the WHO Postpartum Hemorrhage package; and obstetric risk stratification using point-of-care ultrasound (POCUS) and complementary diagnostics for maternal care improvement. We anticipate that this bundle of evidence-based clinical tools and training, reinforced by mentorship, structured checklists, and low-dose high-frequency (LDHF) practice, will significantly reduce perinatal and maternal mortality and morbidity. The bundle will be evaluated using a Hybrid Type 1 effectiveness-implementation design, utilizing routine health information system data, supplemented by project registers, skills assessments, and observations. By aligning with the Ministry of Health’s Child Survival Action Plan, the aim of this project protocol is to provide a sustainable and scalable model for reducing preventable maternal and newborn deaths in resource-constrained settings. Full article

Respiratory syncytial virus (RSV) is considered the leading causative agent of acute lower respiratory infections in infants and young children worldwide, which makes it a major contributor to pediatric morbidity and mortality. Infants are especially susceptible to severe disease in early life, which underlines the urgent need for developing effective immunization strategies against this virus. However, the development of vaccines against RSV has long been associated with significant challenges. For example, initial attempts, especially those involving formalin-inactivated RSV, resulted in vaccine-enhanced respiratory disease upon subsequent infection, which set a significant safety obstacle for future vaccine candidates. Other challenges facing vaccine development against RSV include the short-lived immunity induced by natural infection, lack of clear correlates of immunity, and immune naivety in infants. Recent breakthroughs in structural virology and immunology have provided insights into protective immunity against RSV, especially regarding neutralizing antibodies that recognize the virus in its prefusion conformation of the viral F protein. Among promising vaccine candidates, intranasal live-attenuated vaccines have emerged as especially promising for infant immunization, especially considering their close mimicry of natural infection that can elicit systemic as well as mucosal immunity in the respiratory tract. A newly emerging approach for live-attenuated virus vaccine development is codon-pair deoptimization (CPD), which is based on synthetic recoding that reduces viral replicative capacity while maintaining intact protein sequences and structure. The preclinical results of CPD-based RSV candidates have provided evidence of such vaccines’ ability to elicit robust immunity while maintaining favorable safety profiles. This review addresses the major challenges associated with the development of effective RSV vaccines for infant immunization, with particular emphasis on lessons learned from previous vaccine failures and recent advances in RSV vaccine development, particularly CPD-based attenuation strategies. Full article

Background/Objectives: Chorioamnionitis (CA), an inflammation, with or without infection, involving the amniotic fluid, placenta, fetal membranes or decidua, can significantly impact fetal and neonatal development. This study aimed to determine the prevalence of chorioamnionitis and confirm its correlation with neonatal morbidity and mortality, in a single tertiary center. Methods: This observational, retrospective study was conducted over three years (2019–2021) in a tertiary neonatal intensive care unit, examining 80 preterm infants born at 23–28 weeks of gestation. Spearman rank correlation, χ² tests, and multivariate logistic regression were used to assess associations between chorioamnionitis exposure and neonatal outcomes. Results: Among the 80 newborns analysed, clinical chorioamnionitis was identified in 12 preterm infants, while 65 (81.3%) presented histological chorioamnionitis. No significant association was found between histological chorioamnionitis stage and gestational age at birth (Spearman ρ = −0.15, p = 0.195). Premature rupture of membranes was significantly more frequent in the CA-exposed group (46.2% vs. 13.3%, p = 0.019). In unadjusted analyses, histological chorioamnionitis exposure was associated with higher rates of adverse neonatal outcomes, including early-onset sepsis (46.2% vs. 26.7%), intraventricular haemorrhage (73.8% vs. 60.0%), bronchopulmonary dysplasia (15.9% vs. 6.7%), and retinopathy of prematurity (11.3% vs. 0.0%); however, most of these differences did not reach statistical significance. After multivariate adjustment, histological chorioamnionitis remained independently associated with severe respiratory distress syndrome (adjusted OR 25.84, 95% CI 2.49–268.44, p = 0.006). Mortality was numerically lower in the CA-exposed group (27.7% vs. 46.7%); however, this difference did not reach statistical significance (p = 0.216). Conclusions: Histological chorioamnionitis was independently associated with severe respiratory distress syndrome. Associations with early onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity were observed in unadjusted analyses but were not independently significant after adjustment for perinatal confounders. No significant association was found between chorioamnionitis and neonatal mortality. While clinical diagnostic criteria for chorioamnionitis demonstrated good specificity, their poor sensitivity underscores the urgent need for improved diagnostic tools, including routine histological examination of the placenta. Full article

Background/Objectives: Ventilator-free days (VFDs) are a useful composite measure to assess both survival and duration of mechanical ventilation in critically ill patients. This study aimed to determine the factors associated with (VFDs) in neonates with persistent pulmonary hypertension of the newborn (PPHN) and to compare VFDs according to the etiology and severity of PPHN. Methods: We conducted a retrospective cohort study of neonates diagnosed with PPHN between 2013 and 2023. VFDs were defined as days alive and free of mechanical ventilation within the first 28 days. Severe-to-critical PPHN group was defined as an oxygenation index (OI) > 25. Results: Among 175 neonates, the median (interquartile range [IQR]) VFDs were 20 (9–23) days. The factors independently associated with fewer VFDs included maximum OI > 40 (adjusted hazard ratio [aHR] 3.5, 95% confidence interval [CI]: 2.49–4.9), receiving more than two inotropic drugs (aHR 2.27, 95% CI: 1.49–3.45), acute kidney injury (AKI) (aHR 1.54, 95% CI: 1.1–2.17), and ventilator-associated pneumonia (VAP) (aHR 3.42, 95% CI: 1.8–6.48). The median (IQR) number of VFDs in neonates with PPHN secondary to respiratory distress syndrome (RDS), pneumonia/sepsis, meconium aspiration syndrome, and transient tachypnea of the newborn were 16 (0–22), 17 (7–21), 22 (11–24), and 22 (15–24) d, respectively (p = 0.023). Neonates in the severe-to-critical group had markedly fewer VFDs than those in the mild-to-moderate group (8.5 vs. 22 d, p < 0.001). Conclusions: Infants with PPHN from RDS had the fewest VFDs. A maximum OI > 40, use of multiple inotropic agents, AKI, and VAP were associated with a low number of VFDs. Given the retrospective, single-center design, these findings are associative and hypothesis-generating, requiring prospective multi-center validation. Nonetheless, VFDs remain a comprehensive measure of both mortality and respiratory morbidity in this population. Full article

Background: Esophageal cancer (EC) poses a growing global challenge in the context of an ageing population. Evidence on the role of curative esophagectomy in octogenarians is limited. This study aims to compare the long-term survival and post-operative mortality and morbidity in octogenarians undergoing curative esophagectomy for EC with those in non-octogenarians. Methods: A systematic search was performed on PubMed, Embase, Web of Science and Cochrane Library up to Jan 2026. The inclusion criteria were studies that compared outcomes of esophagectomy for EC between octogenarians and non-octogenarians. Exclusion criteria were single-arm studies and studies using different age cut-offs. Results: There were 18 studies with 73,776 patients (octogenarians n = 6234 and non-octogenarians patients n = 67,542), with smaller subsets of studies being analysed for individual outcomes. The overall incidence of open esophagectomy and minimally invasive esophagectomy (MIE) were 78.4% (n = 459/585) and 21.2% (n = 124/585), respectively, in octogenarians, and 69.8% (n = 3270/4688) and 29.4% (n = 1380/4688), respectively, in non-octogenarians. R0 resection was achieved in 85.2% (n = 1759/2064) of octogenarians and 91.9% (n = 30,764/33,480) of non-octogenarians. Pooled OS was inferior in the octogenarian group compared to the non-octogenarian group (n = 35,441, HR 2.29, 95% CI: 1.38–3.79). Pooled in-hospital mortality, 30-day mortality and 90-day mortality were higher in octogenarians. In terms of post-operative complications, pooled analysis demonstrated a higher overall complication rate in the octogenarian group (n = 6515, OR 1.40, 95% CI: 1.11–1.78), while rates of anastomosis leakage, chylothorax, respiratory complication, surgical site infection and recurrent laryngeal nerve injury were comparable between the two groups. Conclusions: Curative esophagectomy for EC is associated with worse overall survival, mortality and overall post-operative complication rate in octogenarians than non-octogenarians. Further research on the role of MIE in octogenarians should be conducted. Full article

Objective: Delaying postpartum cord clamping may contribute to neonatal circulation by allowing continued placental transfusion. The timing of cord clamping is still debated and is called delayed cord clamping (DCC) if performed more than 30 s after birth. This study evaluated the effect of DCC on the clinical outcomes of preterm infants. Methods: Preterm infants (gestational age < 30 weeks) admitted to our Level 4 neonatal intensive care unit in 2023–2024 were evaluated retrospectively. Delayed cord clamping at postnatal 60 s was practiced when infants were considered stable. The demographic characteristics and morbidities of infants who did and did not have DCC were compared. Results: A total of 156 infants were included in the study. Of these, 70 infants were in the DCC group, and 86 infants were in the non-DCC group. Median gestational age was 28 weeks (interquartile range [IQR]: 26–30 weeks) and 26 weeks (IQR: 25–28 weeks), and median birth weight was 1000 g (IQR: 780–1300 g) and 850 g (IQR: 685–1095 g), respectively (p < 0.001 for both). The DCC group had a higher rate of antenatal steroid (ANS) use (p < 0.001), higher APGAR scores (p < 0.001), and lower rates of intraventricular hemorrhage (IVH) (p < 0.001), respiratory distress syndrome (RDS) (p < 0.001), bronchopulmonary dysplasia (BPD) (p = 0.013), feeding intolerance (p = 0.01), and mortality (p = 0.016) compared to the non-DCC group. Grade 3 IVH was not observed in the DCC group. In logistic regression analysis, not performing DCC was associated with significantly greater odds of IVH (odds ratio [OR]: 2.92, 95% CI: 1.48–5.77, p < 0.01), BPD (OR: 2.25, 95% CI: 1.18–4.29, p = 0.01), RDS (OR: 3.97, 95% CI: 1.86–8.48, p < 0.001), and mortality (OR: 3.44, 95% CI: 1.21–9.81, p < 0.01). However, these differences were not statistically significant after correcting for birth week, birth weight, Apgar score, and ANS. Conclusions: When applied in preterm infants under 30 weeks of gestational age, DCC can promote hemodynamic stability and reduce morbidities such as IVH and RDS. Also, implementing DCC with unstable infants will provide more conclusive information about its effectiveness. Full article

Background/Objectives: Bronchopulmonary dysplasia (BPD) remains a major morbidity among extremely premature infants, with variability in the application of evidence-based interventions between and within neonatal intensive care units (NICUs). We evaluated a multi-component, risk-guided personalized implementation strategy for BPD prevention in a real-world setting. Methods: We conducted a prospective observational study of infants <29 weeks’ gestation at birth admitted to a quaternary NICU. The intervention combined risk stratification and structured longitudinal care planning rounds (LCPRs) that included standardized documentation, multidisciplinary facilitation, and associated continuous quality improvement strategies. Implementation outcomes were assessed using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. Secondary outcomes included care processes, provider-reported measures, and exploratory clinical outcomes. Results: Over six months, 41 infants were included. Risk stratification was consistently applied and all fifteen high-risk infants received LCPR, demonstrating targeted reach. Multidisciplinary participation was broad, with implementation fidelity reflected by consistent screening, structured documentation, and timely care plan execution. Practice standardization was observed, including consistent corticosteroid use (100%), earlier initiation of systemic postnatal steroids (median 16 days), and selective adjunctive therapy use. Providers reported improved teamwork, care coordination, and confidence. Rates of BPD or mortality were comparable between higher-risk infants receiving LCPR and lower-risk infants, despite greater illness severity in the LCPR group. Respiratory severity scores showed a downward trend after implementation, though this did not reach statistical significance (p = 0.07). Strategy use continued beyond the study period indicating early sustainability. Conclusions: A multi-component, risk-guided implementation strategy can be effectively integrated into routine NICU practice, improving care processes while maintaining clinical outcomes in high-risk infants compared with lower-risk infants. Full article

Background/Objectives: Recessive titinopathies caused by biallelic TTN truncating variants (TTNtvs) present a clinically heterogeneous spectrum from fetal demise to late-onset slowly progressive distal muscular dystrophy. Prognostic counseling is challenging due to the vast size of the TTN gene, complex splicing patterns, and differential expression throughout developmental stages and tissues. This paper aims to delineate the regional genotype patterns and clinical characteristics of recessive titinopathies described from the prenatal period onwards to inform genotype–phenotype associations and genetic counseling. Methods: We analyzed clinical and genetic data from a prenatal-onset cohort with biallelic TTNtvs from both previously reported cases and novel cases from our center. To characterize the regional distribution of biallelic variants within this specific cohort, a two-dimensional scatter plot was utilized to map variants onto 10 biological regions (R1–R10) and 55 analytical units (U1–U55). We also performed Fisher’s exact tests on the subset of 50 cases with confirmed survival records to evaluate statistically significant associations between biallelic regional or percent spliced-in (PSI) thresholds combinations and severe clinical endpoints (intrauterine demise or death before 5 years). Results: A total of 96 prenatal cases from 76 unrelated families were analyzed. Decreased fetal movement was the most commonly reported symptom, observed in 81.3% (78/96) of cases, which was followed by arthrogryposis in 45.8% (44/96) and amniotic fluid volume abnormalities in 35.4% (34/96). Additionally, of the 95 cases with known pregnancy outcomes, 25.3% (24/95) resulted in termination and 11.6% (11/95) resulted in intrauterine demise (IUD), while 63.2% (60/95) reached birth with over 16.7% (10/60) being preterm. Among 60 live-born infants, severe postnatal morbidity was high: 45.0% (27/60) experienced respiratory failure, and 33.3% (20/60) died before the age of five. In this cohort, 84.4% (81/96) of cases possessed at least one TTNtv in either the metatranscript-only or A-band regions. The most common biallelic changes involved TTNtvs in both the A-band and metatranscript-only regions, accounting for 35.4% (34/96) of cases, followed by metatranscript-only combined with I-band variants at 16.7% (16/96), regardless of the PSI score of exons. Overall, 83.3% (80/96) had ≥1 variant on low-PSI (<50%) exons, and 19.8% (19/96) had both alleles on these low-PSI exons. In the 50 patients with confirmed survival records, biallelic changes (excluding splice-site variants) affecting both high-PSI (>90%) exons were significantly associated with severe outcomes (intrauterine demise or death before 5 years; exact p = 0.015), whereas the metatranscript-only plus I-band combination conferred a significantly lower risk of lethality before 5 years of age (exact p = 0.001). Conclusions: Our findings add to the accumulating evidence that TTNtvs on low PSl exons or metatranscript-only regions are frequently observed among reported prenatal-onset recessive titinopathy. Health surveillance for heterozygous carriers among family members is warranted due to the substantial risk for adult-onset dilated cardiomyopathy and peripartum cardiomyopathy. Full article