Search Results (159)

Background/Objectives: Neonatal sepsis remains a major cause of morbidity and mortality worldwide, underscoring the critical need for early and accurate diagnostic biomarkers. This study aimed to evaluate the predictive value of the red cell distribution width-to-albumin ratio (RAR) for the diagnosis of neonatal sepsis and to compare its diagnostic performance with the C-reactive protein-to-albumin ratio (CAR) and other hematological parameters. Methods: This retrospective cohort study was conducted in the Neonatology Department of Karadeniz Technical University Faculty of Medicine between January 2015 and June 2025. A total of 874 neonates with a gestational age > 36 weeks were included: 411 with blood culture-confirmed sepsis (108 Gram-negative, 303 Gram-positive) and 463 healthy controls. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis, with optimal cut-off values determined by the Youden index. Results: RAR demonstrated modest diagnostic accuracy for neonatal sepsis, with an area under the curve (AUC) of 0.647 (95% CI: 0.61–0.69), a cut-off value of 5.108, sensitivity of 50.7%, and specificity of 76.7%. RAR was significantly elevated in the Gram-negative group compared with Gram-positive cases and controls (p < 0.001). However, the clinical significance of this subgroup difference requires further investigation. In multivariable logistic regression analysis, RAR remained independently associated with culture-confirmed neonatal sepsis after adjustment for gestational age, birth weight, sex, and mode of delivery (aOR = 2.190, 95% CI: 1.838–2.608, p < 0.001). Among all evaluated markers, CAR achieved the highest diagnostic performance (AUC: 0.981, sensitivity: 88.5%, specificity: 98.7%, PPV: 98.4%, NPV: 90.7%, LR+: 68.47), followed by C-reactive protein (AUC: 0.978), while neutrophil-to-lymphocyte ratio showed the lowest discriminatory ability (AUC: 0.592). Conclusions: RAR showed limited standalone discriminatory performance for culture-confirmed neonatal sepsis, although its association with sepsis remained significant after adjustment for relevant demographic and perinatal factors. CAR demonstrated significantly greater discriminatory performance than RAR. Further studies are needed to determine whether RAR provides incremental value when incorporated into multivariable diagnostic models. Full article

Background/Objectives: Hepatitis A virus (HAV) infection is a relevant biological risk in some occupational settings and has long been discussed as an occupational health concern among municipal waste collection workers. Data on HAV seroprevalence and vaccination history in this occupational group remain limited in Italy. This study investigated HAV seroprevalence, self-reported vaccination history, and factors associated with HAV seropositivity among waste collection workers in Sardinia. Methods: This retrospective cross-sectional study analyzed HAV seroprevalence and self-reported vaccination history among 326 workers in Sardinia, Italy, using occupational health surveillance data (2017–2024). Recorded variables included age, sex, smoking habits, years of service, work setting, vaccination status, and serological results. Chi-square and Mann–Whitney U tests assessed group differences; logistic regression identified factors independently associated with HAV seropositivity. Results: HAV seroprevalence was 44.2%; only 0.9% of participants reported previous HAV vaccination. Multivariable analysis identified older age, but not years of service, as independently associated with HAV seropositivity once age was modeled as a continuous variable—a pattern more consistent with birth-cohort differences in lifetime HAV exposure than with cumulative occupational exposure. Worksite 7 showed a higher prevalence ratio of HAV seropositivity relative to the reference site, but this finding was based on a small subsample and should be considered exploratory; observed worksite-level differences may reflect organizational rather than geographic factors. Conclusions: Older age, rather than occupational tenure, was independently associated with HAV seropositivity among Sardinian waste workers, a pattern consistent with birth-cohort differences in lifetime exposure. The high seroprevalence and very low vaccination uptake highlight the need to strengthen prevention through improved vaccination access, awareness, and better integration of occupational and public health strategies. Full article

Background/Objectives: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) substantially affect quality of life. Previous studies have not evaluated whether the associations between early-life antibiotic exposure and the risks of ASD and ADHD differ according to the antibiotic agents administered during infancy. Methods: This nationwide case–control study used Taiwan’s National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database. The cohort included 1,693,718 term neonates born between 2004 and 2015 and followed through to 2022. For ASD (n = 7265) and ADHD (n = 39,056) cases, antibiotic-exposed children were matched 1:1 with unexposed children based on sex, gestational age, birth weight, and birth year. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results: Oral antibiotic exposure was associated with lower ASD but higher ADHD risk, while parenteral exposure was associated with increased risks of both outcomes. Amoxicillin and erythromycin exposure during the first year of life were associated with lower ASD risk, whereas ampicillin exposure at 4–12 months was associated with higher ASD risk (all p ≤ 0.033). For ADHD, exposure to amoxicillin/clavulanic acid, cefixime, ampicillin, and ampicillin/sulbactam was associated with increased risk, whereas erythromycin, cephalexin, and sulfamethoxazole-trimethoprim were associated with reduced risk (all p < 0.047). Conclusions: Associations between early-life antibiotic exposure and the risks of ASD and ADHD varied according to antibiotic agents, route of administration, and timing of exposure. These findings may help explain inconsistencies among previous studies and inform antibiotic prescribing during infancy. Full article

Background/Objectives: Complete blood count inflammatory indices are widely studied in obstetrics but rarely compared directly. We compared five first-trimester indices, the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), for their associations with preterm birth, examined across its severity. Methods: In a retrospective single-centre cohort of 5003 singleton pregnancies with a first-trimester complete blood count, late (34–36 weeks) and early (<34 weeks) preterm births were analysed separately. The association of each index with preterm birth was assessed by logistic regression, per standard deviation, and by quartile, with adjustments made for maternal age, body mass index, parity, fetal sex, and gestational age at sampling; discrimination was compared using the DeLong test. The birthweight category, classified against the INTERGROWTH-21st standards, was a secondary outcome. Results: After adjustment, all indices except for the PLR were associated with preterm delivery, with similar effects per standard deviation. Among the five indices, the SIRI showed the most consistent association with the severity of preterm birth: its values rose at every step from term to late to early birth. It discriminated these births best (area under the curve 0.600, significantly greater than the SII), and its quartile gradient was steepest, with the odds more than doubling from the lowest to the highest quartile. All five remained weak discriminators, with every area under the curve being below 0.70, and none was associated with the birthweight category. Conclusions: These indices are not standalone predictive tests, but among them, the SIRI, which, unlike the SII, captures the monocyte count, was most closely associated with early, more severe preterm birth, consistent with the role of monocytes in the inflammation of labour. Full article

Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, evidence for sex-specific differences in placental function remains limited. We hypothesized that placental nutrient-sensing signaling activity, amino acid transport capacity, and mitochondrial respiration are higher in male than female placentas. Placentas were collected from 46 women (BMI 18.5–29.9 kg/m²) with uncomplicated pregnancies delivering appropriate-for-gestational-age infants (n = 23 female; n = 23 male). In homogenates of male placentas, the phosphorylation of S6RP (Ser235/236) was increased and total 4E-BP1 protein expression was reduced compared with female placentas, indicating enhanced mTORC1 signaling. In vitro System A amino acid transport activity was also greater in microvillous plasma membranes isolated from male placentas. Placental mitochondrial respiratory capacity was assessed in villous tissue using high-resolution respirometry with carbohydrate and lipid substrate–uncoupler–inhibitor titration (Carb SUIT and Lipid SUIT) protocols on the Oroboros O2k platform. Male placentas exhibited greater maximal oxidative phosphorylation capacity, enhanced complex II-linked respiration, and higher maximal electron transport system capacity compared with female placentas under both carbohydrate- and lipid-supported respiratory conditions. Although placental weight did not differ between sexes, the birth weight-to-placental weight ratio was significantly higher in male pregnancies, consistent with greater placental functional efficiency. In conclusion, placental mTORC1 signaling activity, System A amino acid transport activity, and mitochondrial respiratory capacity are greater in male than female placentas and are associated with greater placental functional efficiency and fetal growth in male pregnancies. Full article

Background/Objectives: Early-life undernutrition may exert lifelong and intergenerational effects on height and weight, but its impact on body shape remains unclear. Using the Great Chinese Famine (1959–1961) as a natural experiment, this study explored the associations between early-life undernutrition and body shape indices across two generations. Methods: We analyzed nine waves of longitudinal data from the China Health and Nutrition Survey (1991–2015), including 5156 participants (F1) born in 1955–1966 and their 2383 biological offspring (F2). F1 famine exposure was classified by birth year; F2 exposure was defined by parental status. Anthropometric indices including body adiposity index (BAI), body roundness index (BRI), waist-to-height ratio (WHtR), conicity index (COI), and a body shape index (ABSI) were derived from repeated measurements. Age-specific fitted curves of these indices were compared across exposure groups using mixed-effects models with fractional polynomials of age. Results: Fetal famine exposure was modestly associated with lower COI and ABSI in adulthood, particularly among men. Childhood famine exposure was significantly linked to lower BAI (−0.40), BRI (−0.26), WHtR (−0.0140), COI (−0.0188), and ABSI (−0.0008), with stronger associations in men (all P for sex interaction <0.05). Intergenerationally, maternal childhood exposure was associated with higher offspring BAI, whereas paternal childhood exposure was associated with lower BAI, BRI, WHtR, COI, and ABSI. Conclusions: Famine exposure showed more pronounced associations with body shape in men, and maternal and paternal exposures displayed different intergenerational patterns. These exploratory findings suggest the possibility that early-life undernutrition may relate to long-term phenotypes in a sex-specific manner, though this requires independent replication. Full article

The objectives of this study were to evaluate the effects of different dietary omega-6 to omega-3 (n-6:n-3) fatty acid ratios during timed artificial insemination (TAI) on reproductive responses, luteal development, and offspring characteristics in lactating dairy cows. Holstein cows (n = 60) averaging 109 ± 10 days in milk (DIM) were randomly assigned to receive either a greater n-6:n-3 diet or a lower n-6:n-3 diet for 42 days. All cows were synchronized using a modified Ovsynch protocol. Although synchronized ovulation rates and pregnancy outcomes were not significantly affected by treatment, cows fed the lower n-6:n-3 ratio exhibited significantly greater corpus luteum (CL) volume and cross-sectional area on days 11 and 14 post-TAI, indicating enhanced luteal development. Pregnancy rates following the first AI and cumulative AI, as well as the number of services per conception, did not differ between treatments. However, cows fed the lower n-6:n-3 ratio tended to produce a greater proportion of female offspring (66.67% vs. 42.90%; p = 0.09). In addition, calves born to cows receiving the lower n-6:n-3 ratio had greater birth weights than calves born to cows fed the greater n-6:n-3 ratio diet. Additionally, the lower n-6:n-3 diet tended to increase milk yield and significantly increased lactose and solids-not-fat yields. In conclusion, a lower dietary n-6:n-3 ratio during a TAI program enhanced luteal development, tended to increase the proportion of female offspring and increased calf birth weight. These findings suggest that reducing the dietary n-6:n-3 ratio during the breeding period may enhance luteal development and may influence offspring sex ratio and calf birth weight in lactating dairy cows. Full article

Background/Objectives: Osteoporosis-related fragility fractures are sentinel events that should trigger timely secondary prevention, yet post-fracture care remains inconsistent. Leveraging the NIH All of Us Research Program, we quantified initiation of osteoporosis pharmacotherapy after fragility fracture and explored associations by age, sex at birth, race, and ethnicity. Methods: Retrospective cohort study using All of Us Controlled Tier data (v8) included adults aged 45 to 100 years with an index fragility fracture using prespecified OMOP concept sets intended to capture fractures commonly associated with osteoporosis. A new-user design excluded participants with any osteoporosis pharmacotherapy in the 365 days before fracture; participants required at least 180 days of follow-up. The primary outcome was initiation of osteoporosis pharmacotherapy (bisphosphonates, denosumab, or anabolic agents) within 180 days. Secondary outcomes were completion of dual-energy x-ray absorptiometry (DXA) and bone-health laboratory testing within 180 days. Multivariable logistic regression estimated adjusted odds ratios (OR) for each outcome by age at fracture, sex at birth, race, and ethnicity. Results: Among 1492 eligible participants, 87 initiated pharmacotherapy within 180 days (5.83%). After adjustment, older age was associated with higher odds of initiation (OR 1.04 per year; 95% CI 1.02 to 1.05). Male participants had markedly lower odds of pharmacotherapy initiation (OR 0.20; 95% CI 0.11 to 0.37) and DXA screening (OR 0.22; 95% CI 0.15 to 0.32) compared with female participants. In exploratory adjusted models, we did not detect an independent association between race and pharmacotherapy initiation (White vs. Black/African American OR 1.01; 95% CI 0.49 to 2.09), while White participants had higher odds of DXA screening than Black/African American participants (OR 1.79; 95% CI 1.02 to 3.28). Conclusions: In this diverse national EHR-based cohort, initiation of osteoporosis pharmacotherapy after fracture was uncommon, highlighting a substantial secondary prevention gap. In exploratory adjusted models, male sex was associated with lower odds of pharmacotherapy initiation and DXA receipt, while White participants had higher odds of DXA receipt than Black participants. System-level post-fracture pathways, including fracture liaison services and EHR-based prompts, may improve equitable identification and treatment of osteoporosis for All of Us participants and their communities. Full article

Background and Aims: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of mortality worldwide, with lipid abnormalities playing a central role in disease development. While the causal role of low-density lipoprotein cholesterol (LDL-C) in ASCVD is well-established, the long-term population impact of combined lipid profiles, particularly the HDL-C/LDL-C ratio, remains less clearly quantified. This study aimed to estimate the lifetime burden of cardiovascular outcomes associated with different lipid risk profiles using a patient-level simulation framework. Methods: The authors analyzed projected lifetime ASCVD events across four HDL-C/LDL-C risk strata, ranging from low (≥0.45) to very high (<0.25), using the National Health Model Database of Projected and Estimated Outcomes (NHM-DPEO)—a digital twin of national healthcare systems built from multiple data sources, including national health and demographic statistics and estimates from the relevant literature. The framework is structured as a patient-level simulation model that projects individual health trajectories over a lifetime horizon. Model outputs were assessed for plausibility by comparison with published epidemiological estimates. Results: The NHM simulation revealed a strong, graded relationship between lipid profiles and cardiovascular survival. Life expectancy declined from 80.2 years in the lowest risk group (HDL-C/LDL-C ≥ 0.45) to 63.0 years in the very-high-risk group (HDL-C/LDL-C < 0.25), a reduction of 17.2 years, with 13.7 fewer QALYs. Similarly, participants with LDL-C > 5.0 mmol/L had a life expectancy 13.4 years shorter than those with LDL-C < 3.1 mmol/L. The burden of ASCVD increased exponentially with worsening lipid ratios: MI events rose from 5000 to 73,090 per 100,000 births, with onset in the highest risk group occurring as early as age 20. Ischaemic heart disease followed a similar pattern, showing up to 92% of events attributable to elevated lipid risk. While ischaemic stroke risk displayed a more complex pattern due to earlier MI mortality in high-risk groups, overall cardiovascular mortality and lifetime event burden were dominated by LDL-driven disease. These findings demonstrate that sustained LDL-C reduction and balanced HDL-C/LDL-C ratios confer substantial survival benefits across both sexes and all age groups. Conclusions: This study shows that lipid balance has a decisive influence on cardiovascular survival. Sustained LDL-C reduction and favourable HDL-C/LDL-C ratios markedly extend life expectancy and delay the onset of MI and IHD. The magnitude of this survival benefit highlights the need for early and continuous lipid control as a cornerstone of ASCVD prevention. The NHM quantifies these lifetime effects, offering valuable insights for targeted strategies that improve both longevity and quality of life. Full article

Background and Objectives: The double burden of malnutrition (DBM), characterized by the coexistence of malnutrition and overweight within the same household, has become a significant public health concern in low- and middle-income countries. Tanzania is undergoing a nutritional transition marked by persistent child malnutrition alongside increasing maternal overweight. This study examined socio-demographic, maternal, and child-level factors associated with DBM among children under five years in Tanzania. Methods: This cross-sectional study used data from the 2022 Tanzania Demographic and Health Survey, including a weighted sample of 5744 children under five and their mothers aged 15–49 years. DBM was defined as the presence of child malnutrition, measured using the Composite Index of Anthropometric Failure (CIAF), in households where the mother was overweight or obese. Bivariate chi-square tests and binary logistic regression analyses were conducted in STATA 17. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were estimated to identify predictors of DBM. Results: DBM was more prevalent in rural areas. Significant predictors included birth order (AOR = 0.611, p = 0.030), child sex (AOR = 0.708, p = 0.011), perceived birth size (AOR = 0.270, p = 0.004), child age (AOR = 0.474, p < 0.001), maternal age (AOR = 0.599, p = 0.045), and maternal education (AOR = 0.604, p = 0.035). Higher maternal education reduced the likelihood of DBM, while firstborn male and small-sized children were at greater risk. Conclusions: DBM in Tanzania is influenced by both biological and socio-demographic factors. Integrated, multi-sectoral interventions targeting maternal education, prenatal care, and optimal maternal nutrition are essential to reduce DBM and achieve global malnutrition reduction targets. Full article

Aims: This study aimed to examine the associations between both birth weight (BW) and body mass index (BMI)/waist circumference (WC) measured at ages 7–10 years, and adolescent overweight (OW)/obesity (OB), and central OB at ages 11–13 years. Methods: Longitudinal data were collected from children’s and parents’ questionnaires. Anthropometric data were obtained from health check-ups. BW (kg) was categorized into three groups: <3.0, 3.0–3.9 and ≥4.0 (macrosomia). Underweight (UW)/normal weight (NW), OW and OB were defined based on sex- and age-specific reference values for Chinese children. Central OB was identified using the sex-specific waist-to-height ratio (WHtR) cutoffs. Results: Of the 1204 children, 14.5% had a BW < 3.0 and 15.6% had macrosomia. The rates of OB and central OB were 10.13% and 28.32%, respectively, among children aged 7–10 years and 6.23% and 23.34%, respectively, among those aged 11–13 years. An increasing BW z-score was associated with higher odds of OW/OB in girls aged 11–13 years. Childhood BMI and WC z-scores were associated with higher odds of OW/OB and central OB, respectively, at ages 11–13 years. Childhood OW/OB and central OB were associated with a higher risk of OW/OB and central OB, respectively, at ages 11–13 years. Conclusions: BW was modestly associated with OW/OB in girls. Childhood BMI was the strongest predictor of OW/OB, while childhood WC was a strong and significant predictor of central OB in early adolescence. These findings highlight that early school age is a critical period for risk identification and the implementation of future preventive strategies. Full article

Background/Objectives: Fetal growth restriction (FGR) represents a model of adverse intrauterine programming associated with an increased risk of cardiometabolic disorders later in life. We examined the relationships between birth weight, catch-up growth, adipokine signaling, and early cardiometabolic risk in adolescents. Methods: This cross-sectional study included 80 term-born adolescents (40 FGR, 40 controls) matched for age and sex. Anthropometry, blood pressure, lipid profile, fasting glucose, adipokines (leptin, adiponectin), and ghrelin levels were assessed. Associations between birth weight, growth rate, adipokines, and cardiometabolic outcomes were analyzed. Results: Birth weight was not associated with adiposity, lipid profile, blood pressure, or glycemic status (p > 0.05). In contrast, catch-up growth in the FGR group was correlated with increased BMI (ρ = 0.680, p < 0.001), central adiposity (ρ = 0.714, p < 0.001), systolic blood pressure (ρ = 0.448, p = 0.0037) and diastolic blood pressure (ρ = 0.325, p = 0.0409). Mediation analyses showed that the current BMI largely explains the associations between catch-up growth and cardiometabolic risk, systolic blood pressure, and waist circumference (β = 2.832 kg/m² per 1-unit increase in ΔZ; p < 0.001). The hypertensive effect of catch-up growth was amplified in overweight/obese adolescents (β = 8.13 mmHg; p = 0.006). Catch-up growth was independently associated with higher leptin (β = 220 ng/L; p = 0.022) and a higher leptin/ghrelin ratio (β = 2.330; p = 0.034). Conclusions: Postnatal growth acceleration, rather than fetal size alone, drives early cardiometabolic susceptibility following FGR through adiposity-mediated and endocrine pathways. Full article

Background/Objectives: In this study, we aimed to evaluate whether neonatal ischemia-modified albumin (IMA) and umbilical venous cord blood gas parameters are associated with antenatal markers of fetal well-being, including the umbilical coiling index (UCI) and umbilical artery (UA) and middle cerebral artery (MCA) Doppler indices. Methods: For this prospective observational study, sixty-five low-risk term pregnancies (≥37 weeks) were included. Prenatal ultrasound was used to measure the UCI and UA/MCA Doppler indices. At delivery, umbilical venous cord blood gas and serum IMA analyses were performed. Maternal and neonatal data (birth weight, 5 min Apgar score, NICU admission, sex, and delivery mode) were recorded, and correlations and group comparisons were performed (p < 0.05). Results: The UCI ranged from 0.210 to 0.471 coil/cm (mean 0.337). The UA and MCA Doppler indices were within the reference ranges. The UCI showed no significant correlation with umbilical venous blood gas values, IMA, UA/MCA Doppler indices, gestational age/weeks, or 5 min Apgar score. The UA S/D ratio and UA resistive index (RI) were negatively correlated with birth weight (p < 0.05). Umbilical venous pH was positively correlated with the 5 min Apgar score, whereas venous pCO₂ was negatively correlated with the 5 min Apgar score (both p < 0.05). Newborns with venous pH < 7.32 had higher cesarean delivery rates and higher rooming-in rates. Newborns admitted to the NICU had higher mean UA systolic velocity/diastolic velocity (S/D) and UA pulsatility index (PI) and lower venous pH. Conclusions: In low-risk term pregnancies, the UCI was not associated with cord blood gas parameters, IMA, or UA/MCA Doppler indices. These results suggest that the UCI may have limited clinical utility as a predictor of early neonatal acidosis or oxidative stress in a strictly low-risk population. Full article

This study evaluated reproductive parameters, parturition characteristics, and early neonatal survival in 42 pregnant Labrador Retriever bitches and their 346 puppies between June and December 2024. The mean age of the bitches was 4.06 ± 1.59 years, and their average body weight was 33.14 ± 3.72 kg. Litter size averaged 8.24 ± 1.88 puppies, with an almost equal sex ratio (50.2% males; 49.8% females). Mean labour duration was 743 min, and intervals between successive births shortened initially before increasing in late parturition. In 57.1% of litters, all puppies were born alive. Early neonatal mortality was low: 0.6% within the first hour and 8.4% by day seven postpartum. A significant association was detected between prolonged parturition and a higher percentage of stillborn puppies (p = 0.001). Maternal body weight showed a substantial negative correlation with the number of live-born puppies (r = −0.554) and a positive correlation with stillbirths (r = 0.499). The exploratory Q coefficient, expressing the ratio between puppy and maternal body weight, differed significantly across survival categories (p = 0.0027), with surviving puppies displaying the highest ratio. Birth order significantly influenced mortality (p = 0.008), with a marked increase from the sixth puppy onwards. No effect of bitch age was observed on parturition length or puppy birth weight (p > 0.05). Overall, these findings suggest that maternal body weight, parturition duration, and birth order are important determinants of neonatal outcomes in Labrador Retrievers and may assist in improving perinatal management practices. Full article

Background and Objectives: The volume–outcome relationship in congenital heart surgery (CHS) has been widely reported internationally, but systematic nationwide evidence from Korea remains limited. Given the concentration of high-volume centers in the Seoul Capital Area (SCA), we aimed to examine whether hospital surgical volume was associated with short-term mortality and to what extent regional disparities could be explained by differences in surgical volume. Materials and Methods: We conducted a nationwide retrospective cohort study of 31,150 patients who underwent CHS in 91 hospitals in Korea between 2002 and 2021 using National Health Insurance claims data. Hospitals were classified by location (SCA vs. non-SCA). Annual surgical volume was defined using two approaches, (i) above vs. below the overall mean annual volume (17.1 cases per hospital), and (ii) three categories (≤20, 21–40, and >40 cases/year). The primary outcome was 30-day mortality. Multivariable logistic regression adjusted for case mix, including J-STAT category, sex, hospital type, age, prematurity, and low birth weight. Hospital-level variation was further evaluated using generalized linear mixed models with random hospital intercepts, and intraclass correlation coefficients (ICCs) were estimated to quantify between-hospital variation and the explanatory contribution of surgical volume. Results: Overall 30-day mortality was 1.99%, with higher mortality observed in non-SCA hospitals compared with SCA hospitals (3.19% vs. 1.57%). After adjustment, lower annual surgical volume was strongly associated with higher 30-day mortality. Compared with hospitals performing >40 cases/year, the adjusted odds ratios were 4.13 (95% CI, 3.30–5.17) for hospitals performing 21–40 cases/year and 4.95 (95% CI, 3.98–5.95) for those performing ≤20 cases/year. In multilevel analyses, annual surgical volume accounted for 54% of the between-hospital variation in 30-day mortality. Adjustment for surgical volume substantially attenuated the regional disparity, with the odds ratio for non-SCA versus SCA hospitals decreasing from 2.12 (95% CI, 1.80–2.49) to 1.14 (95% CI, 0.95–1.37). Conclusions: A strong volume–outcome relationship exists in congenital heart surgery in Korea, with excess mortality concentrated in low-volume hospitals rather than regional location itself. Regional disparities in outcomes appear largely attributable to the uneven distribution of surgical volume. Strategies focused on service consolidation and strengthened referral to high-volume centers may be effective in reducing inter-hospital variation and improving national outcomes in pediatric cardiac surgery. Full article