Surgical outcomes of very-early-onset ulcerative colitis: retrospective comparative study with older pediatric patients.

PURPOSE: The study compares the surgical outcomes of very-early-onset ulcerative colitis (VEO-UC), which is a rare disease diagnosed in pediatric patients < 6 years, with those of older pediatric patients with ulcerative colitis (UC). METHODS: A retrospective observational study of 57 pediatric patients with UC was conducted at a single center. The study compared surgical complications and postoperative growth between the two groups. RESULTS: Out of the 57 patients, 6 had VEO-UC, and 5 of them underwent total colectomy. Compared with the surgical cases of older patients with UC (n = 6), the rate of postoperative complications in patients with VEO-UC (n = 5) was not significantly different, except for high-output ileostomy (80% vs. 0% at 3 weeks postoperatively, p = 0.02). The rate of postoperative central venous catheter (CVC) placement at > 90 days was higher in patients with VEO-UC (100% vs. 17%, p = 0.02). The median change in the Z-score of height before and 2 years after colectomy was not significantly different between VEO-UC and older patients (1.1 vs. 0.3, p = 0.13). CONCLUSION: With regard to complications and outcomes, total colectomy for VEO-UC patients and that for older pediatric UC patients is comparable. However, high-output ileostomy and the long duration of CVC placement may pose management challenges.

Risk Factors for Preoperative Pneumothorax in Neonates With Isolated Left-Sided Congenital Diaphragmatic Hernia: An International Cohort Study.

BACKGROUND: We aimed to investigate the clinical characteristics and outcomes of patients with isolated left-sided congenital diaphragmatic hernia (CDH) who developed preoperative pneumothorax and determine its risk factors. METHODS: We performed an international cohort study of patients with CDH enrolled in the Congenital Diaphragmatic Hernia Study Group registry between January 2015 and December 2020. The main outcomes assessed included survival to hospital discharge and preoperative pneumothorax development. The cumulative incidence of pneumothorax was estimated by the Gray test. The Fine and Gray competing risk regression model was used to identify the risk factors for pneumothorax. RESULTS: Data for 2858 neonates with isolated left-sided CDH were extracted; 224 (7.8%) developed preoperative pneumothorax. Among patients with a large diaphragmatic defect, those with pneumothorax had a significantly lower rate of survival to discharge than did those without. The competing risks model demonstrated that a patent ductus arteriosus with a right-to-left shunt flow after birth (hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.21-2.63; p = 0.003) and large defects (HR: 1.65; 95% CI: 1.13-2.42; p = 0.01) were associated with an increased risk of preoperative pneumothorax. Significant differences were observed in the cumulative incidence of pneumothorax depending on defect size and shunt direction (p < 0.001). CONCLUSIONS: Pneumothorax is a significant preoperative complication associated with increased mortality in neonates with CDH, particularly in cases with large defects. Large diaphragmatic defects and persistent pulmonary hypertension were found to be risk factors for preoperative pneumothorax development. LEVEL OF EVIDENCE: LEVEL Ⅲ Retrospective Comparative Study.

Impaired Aortic Growth in Neuroblastoma Patients After Intensive Treatment.

PURPOSE: This study evaluated the abdominal aortic diameter in high-risk neuroblastoma (NB) patients and the risk of aortic narrowing following intensive treatment. METHODS: We measured the aortic diameter at four specific levels of the abdominal aorta (diaphragmatic crus, celiac axis, and the root of the superior (SMA) and inferior (IMA) mesenteric arteries) on contrast CT scans. The control group consisted of 56 children with non-oncologic disorders, while the NB group included 35 patients with high-risk abdominal NB. We used regression analysis of age and aortic diameter to determine the regression formula for each level in each group and performed intergroup comparisons using t-test. RESULTS: We evaluated a total of 160 contrast-enhanced CTs performed in the 35 eligible cases. The aortic diameter of pretreated NB patients was not significantly different from the controls. After receiving any treatment, the aortic diameter was significantly smaller in the NB group (p < 0.01 each). Patients who underwent radical surgery, particularly gross total resection (n = 26), had smaller aortic diameters at all levels compared to controls (p < 0.01 each). Patients treated with radiotherapy (RT) had smaller aortic diameters than controls. External beam radiotherapy (EBRT) patients (n = 24) had smaller aortic diameters at all levels except the celiac axis (crus, SMA, IMA; p < 0.01 each), and intraoperative radiotherapy (IORT) ± EBRT patients (n = 5) had smaller aortic diameters at all levels (p < 0.01 each). CONCLUSION: Patients with NB may experience impaired development of the abdominal aorta after multimodal therapy, particularly after RT. Close observation and long-term follow-up is essential to monitor for catastrophic vascular complications. LEVEL OF EVIDENCE: LEVEL III.

Influence of surgical volume on the mortality and morbidity of gastrointestinal perforation in children.

PURPOSE: To clarify the influence of surgical volume on the mortality and morbidity of gastrointestinal perforation in children in Japan. METHODS: We collected data on pediatric patients with gastrointestinal perforation between 2017 and 2019, from the National Clinical Database. The surgical volumes of various institutions were classified into three groups: low (average number of surgeries for gastrointestinal perforation/year < 1), medium (≥ 1, < 6), and high (≥ 6). The observed-to-expected (o/e) ratios of 30-day mortality and morbidity were calculated for each group using an existing risk model. RESULTS: Among 1641 patients (median age, 0.0 years), the 30-day mortality and morbidity rates were 5.2% and 37.7%, respectively. The 30-day mortality rates in the low-, medium-, and high-volume institutions were 4.9%, 5.3%, and 5.1% (p = 0.94), and the 30-day morbidity rates in the three groups were 26.8%, 39.7%, and 37.7% (p < 0.01), respectively. The o/e ratios of 30-day mortality were 1.05 (95% confidence interval [CI] 0.83-1.26), 1.08 (95% CI 1.01-1.15), and 1.02 (95% CI 0.91-1.13), and those of 30-day morbidity were 1.72 (95% CI 0.93-2.51), 1.03 (95% CI 0.79-1.28), and 0.95 (95% CI 0.56-1.33), respectively. CONCLUSION: Surgical volume does not have significant impact on the outcomes of pediatric gastrointestinal perforation in Japan.

Establishment of a quantitative assessment model and web-based calculation tool for the skeletal muscle index in children.

BACKGROUND & AIMS: The skeletal muscle index (SMI) is widely used in adults. The reference values for SMI in children are inadequate and require validation in pediatric patients for clinical usefulness. Therefore, this study developed a quantitative assessment model for SMI in children using standard deviation (SD) curves and validated the model's utility and generalizability. METHODS: We examined three compartments of the abdominal skeletal muscle region. SMI was calculated as skeletal muscle area divided by height squared for each compartment (PMI, psoas muscle index; PSMI, paraspinal muscle index; TSMI, total skeletal muscle index). The optimal model was generated using random grouping methods (training and testing), polynomial regression analysis, and the mean squared error evaluation methods. The generated model was validated with previously published SMI data and clinical data of patients with inflammatory bowel disease. RESULTS: The data of 474 children were analyzed. The previously reported SMI reference values overlapped well with our model. In patients with inflammatory bowel disease, the mean (SD) Z-scores for SMI were low in boys (PMI, -1.15 [1.11]; PSMI, -1.31 [1.07]; TSMI, -0.84 [0.91]) and girls (PMI, -1.22 [1.08]; PSMI, -1.44 [1.19]; TSMI, -0.74 [1.16]). Furthermore, SMI was positively correlated with body weight, body mass index, and serum albumin level, a nutritional marker, and negatively correlated with erythrocyte sedimentation rate, an inflammatory marker. CONCLUSION: We established a quantitative assessment model for SMI and validated the model's generalizability and clinical usefulness. We generated an easy-to-use calculation tool for Z-scores from skeletal muscle area obtained from computed tomography images, age, and height information; it has been made publicly available (http://square.umin.ac.jp/ped-muscle-calc/index.html).

Outcomes of adult native liver survivors with biliary atresia: the current situation in Japan.

PURPOSE: This study aimed to elucidate the difficulties faced by adult native liver survivors with biliary atresia (BA) in Japan. METHODS: A single-center, retrospective, observational study of 57 adult patients with BA was conducted. The clinical course of BA was compared between native liver survivors and non-survivors who reached adulthood. Indications and outcomes of liver transplantation (LT) among non-survivors were assessed. RESULTS: A significantly larger portion of non-survivors (n = 10) met the criteria for LT (p < 0.001) and received treatment for portal hypertension after reaching 20 years of age (p < 0.01) compared with the survivors. Causes of death included liver cirrhosis (n = 8), graft failure of living donor liver transplantation (LDLT) (n = 1), and hepatocarcinoma (n = 1). Two of the non-survivors who died of liver cirrhosis had no indication for LT because of alcohol dependence and uncontrolled infection. An appropriate donor candidate could not be found for the five patients who opted for LDLT. All six patients waitlisted for deceased donor liver transplantation (DDLT) died after a median waiting period of 17 months. CONCLUSION: Adult BA patients in Japan have limited options for LT, mainly owing to low donor candidate availability for LDLT and a low prevalence of DDLT.

Frequency of infiltrating regulatory T-cells in the portal tract of biliary atresia.

PURPOSE: Immunological abnormalities have been hypothesized as a pathogenesis of biliary atresia (BA). We previously investigated the frequency and function of circulating regulatory T-cells (Tregs) and reported no differences compared to controls. However, the local Treg profile remains uncertain. We aimed to investigate the frequency of Tregs in BA liver tissues. METHODS: The number of lymphocytes, CD4+ cells, and CD4+FOXP3+ Tregs infiltrating the portal tract and the percentage of Tregs among CD4+ cells of BA and control patients were visually counted. The correlation between these data and clinical indicators was also examined. RESULTS: The number of lymphocytes, CD4+ cells, and CD4+FOXP3+ Tregs was higher in the BA group. However, the percentage of Tregs among CD4+ cells was similar in both groups. Each parameter was correlated with serum γ-GTP, but there was no clear association with liver fibrosis, jaundice clearance, and native liver survival. CONCLUSION: The number of Tregs infiltrating the portal tract was higher in BA patients. However, the infiltration of lymphocytes was also generally increased. Tregs appear to be unsuccessful in suppressing progressive inflammation in BA patients, despite recruitment to local sites. Investigation of Treg function in the local environment is warranted.

Assessment of pulmonary artery size at birth as a prognostic factor in congenital diaphragmatic hernia: results of a multicenter study in Japan.

OBJECTIVE: To assess the reliability of pulmonary artery (PA) parameters as a prognostic marker in neonates with isolated left-sided congenital diaphragmatic hernia (IL-CDH). STUDY DESIGN: A retrospective cohort study conducted by the Japanese CDH Study Group (JCDHSG). RESULTS: 323 IL-CDH patients registered with the JCDHSG were included. 272 patients survived to 90 days of age. Right PA (RPA) and left PA (LPA) diameters and pulmonary artery index (PAIndex) at birth were significantly larger in survivors. The cutoff values of RPA and LPA diameters and PAIndex for survival up to 90 days were 3.2 mm, 2.8 mm and 83.7, respectively, and logistic regression analysis showed that these were significantly related to survival. Multiple logistic regression analysis showed that both the PA parameters and liver herniation were significantly related to survival. CONCLUSIONS: The three PA parameters at birth can predict clinical outcomes and are considered as independent risk factors of liver herniation.

Gastric tumor mimicking bronchial tissue associated with a laryngotracheoesophageal cleft: a case report.

BACKGROUND: Laryngotracheoesophageal cleft (LTEC) is a rare disease in which the larynx and trachea communicate posteriorly to the esophagus. It is often associated with other congenital malformations, particularly gastrointestinal anomalies. Herein, we report a case of LTEC associated with a gastric polypoid lesion in bronchial tissue. CASE PRESENTATION: A gastric mass was detected in a male fetus since week 21 of gestation using fetal ultrasonography. Esophagogastroduodenoscopy performed after birth revealed a pedunculated polypoid lesion of the gastric fornix. The patient experienced frequent vomiting and aspiration pneumonia, which persisted after nasoduodenal tube feeding. Communication between the airway and esophagus was suspected. Laryngoscopy performed 30 days later revealed an LTEC (type III). Partial gastrectomy was performed when the patient was 93 days of age. Histopathological examination revealed tumor consisting of cartilage tissue covered with a layer of respiratory epithelium. CONCLUSION: The gastric tumor associated with LTEC exhibited structures mimicking bronchial tissue. LTEC occurs because of foregut maldevelopment, and the tumorous respiratory tissue in the stomach may have been formed from the same abnormal foregut development event as LTEC.

Neonatal outcomes of congenital diaphragmatic hernia in full term versus early term deliveries: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to review the optimal timing of delivery at term for neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). We reviewed the literature up to December 19, 2022 using MEDLINE and the Cochrane Library databases. The inclusion criteria were original articles, comparative studies of CDH neonates delivered at an early term (37-38 weeks of gestation) and at full term (39 weeks of gestation or later), and comparative studies investigating outcomes of CDH neonates. Six studies met the inclusion criteria, including 985 neonates delivered at an early term and 629 delivered at full term. The cumulative rate of survival to discharge showed no significant difference between CDH neonates delivered at an early term (395/515; 76.7%) or at full term (345/467; 73.9%) (risk ratio [RR] 1.01; 95% confidence interval [CI], 0.89-1.16; p = 0.85). Furthermore, the number of neonates requiring oxygen therapy at discharge was not significantly different between CDH neonates delivered at an early term (32/370; 8.6%) and at full term (14/154; 9.1%) (RR, 0.99; 95% CI, 0.36-2.70; p = 0.99). Therefore, the optimal timing of delivery at term for neonates with CDH remains unclear.

Outcomes of congenital diaphragmatic hernia among preterm infants: inverse probability of treatment weighting analysis.

OBJECTIVES: To evaluate the survival and intact-survival rates among preterm infants with congenital diaphragm hernia (CDH). STUDY DESIGN: Multicenter retrospective cohort study of 849 infants born between 2006 and 2020 at 15 Japanese CDH study group facilities. Multivariate logistic regression analysis adjusted using inverse probability treatment weighting (IPTW) method was used. We also compare trends of intact-survival rates among term and preterm infants with CDH. RESULTS: After adjusting using the IPTW method for CDH severity, sex, APGAR score at 5 min, and cesarean delivery, gestational age and survival rates have a significantly positive correlation [coefficient of determination (COEF) 3.40, 95% confidence interval (CI), 1.58-5.21, p value <0.001] and higher intact-survival rate [COEF 2.39, 95% CI, 1.73-4.06, p value 0.005]. Trends of intact-survival rates for both preterm and term infants had significantly changed, but improvement in preterm infants was much smaller than in term infants. CONCLUSION: Prematurity was a significant risk factor for survival and intact-survival among infants with CDH, regardless of adjustment for CDH severity.

Intraoperative Transpyloric Tube Insertion for Congenital Diaphragmatic Hernia: Analysis of Japanese Study Group Data.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe congenital disease. Some CDH infants suffer from gastro-esophageal reflux disease (GERD), even after surgical correction of gastric position. A transpyloric tube (TPT) is inserted into CDH patients under direct observation intraoperatively in some hospitals in Japan to establish early enteral feeding. This strategy avoids gastric expansion to maintain a better respiratory condition. However, it is unclear whether the strategy has a secure effect for patient prognosis. This study aimed to evaluate the effectiveness of intraoperative TPT insertion on enteral feeding and postoperative weight gain. METHODS: The Japanese CDH Study Group database was used to identify infants with CDH born between 2011 and 2016, who were then divided into two groups: the TPT group and gastric tube (GT) group. In the TPT group, infants underwent intraoperative TPT insertion; postoperative insertion/extraction of TPT was irrelevant to the analysis. Weight growth velocity (WGV) was calculated using the exponential model. Subgroup analysis was performed using Kitano's gastric position classification. RESULTS: We analyzed 204 infants, of which 99 and 105 were in the TPT and GT groups, respectively. Enteral nutrition (EN) in the TPT and GT groups was 52 ± 39 and 44 ± 41 kcal/kg/day (p = 0.17) at age 14 days (EN14), respectively, and 83 ± 40 and 78 ± 45 kcal/kg/day (p = 0.46) at age 21 days (EN21), respectively. WGV30 (WGV from day 0 to day 30) in the TPT and GT groups was 2.3 ± 3.0 and 2.8 ± 3.8 g/kg/day (p = 0.30), respectively, and WGV60 (WGV from day 0 to day 60) was 5.1 ± 2.3 and 6.0 ± 2.5 g/kg/day (p = 0.03), respectively. In infants with Kitano's Grade 2 + 3, EN14 in the TPT and GT groups was 38 ± 35 and 29 ± 35 kcal/kg/day (p = 0.24), respectively, EN21 was 73 ± 40 and 58 ± 45 kcal/kg/day (p = 0.13), respectively, WGV30 was 2.3 ± 3.2 and 2.0 ± 4.3 g/kg/day (p = 0.76), respectively, and WGV60 was 4.6 ± 2.3 and 5.2 ± 2.3 g/kg/day (p = 0.30), respectively. CONCLUSION: Intraoperative TPT insertion did not improve nutritional intake and WGV30. WGV60 in TPT was less than that in GT. In Grade 2 + 3 subgroup analysis, TPT also had no advantage. We could not recommend routine TPT insertion at surgery. LEVEL OF EVIDENCE: III.

Establishment and validation of reference values for abdominal skeletal muscle compartments in children.

BACKGROUND & AIMS: Sarcopenia, resulting from skeletal muscle loss, is a serious concern in children, for whom nutrition and physical activity are essential for growth. In sarcopenia research, the skeletal muscle mass is often obtained from computed tomography (CT) cross-sectional images in both adults and children; however, the method of evaluating skeletal muscle using CT, especially the area range to be measured, has not yet been validated in children. The aim of this study is to establish reference values for three compartments of the abdominal skeletal muscle area (aSMA) obtained from cross-sectional CT images, and to validate the differences among them by assessing correlations with physical development. METHODS: We conducted a single-centre, retrospective, cross-sectional study and included patients aged 1-17 years who underwent abdominal CT at Chiba University Hospital from 2007 to 2020. Patients with chronic diseases such as malignant tumours and inflammatory bowel disease were excluded from the analysis. aSMA was obtained from CT cross-sections at the lumbar L3-L4 intervertebral disc level by dividing it into three compartments: the psoas muscle area (PMA), paraspinal muscle area (PSMA), and total skeletal muscle area (TSMA). Quartile regression curves by sex and muscle compartment were generated using non-crossover and nonparametric regression quantile estimation. The correlation between each compartment of aSMA with height and weight was assessed using Spearman's rank correlation coefficient. RESULTS: We analysed the abdominal CT images of 593 children (male: n = 335, female: n = 258) and generated curves predictive for the 5th, 25th, 50th, 75th, and 95th percentiles for each compartment of aSMA by sex. In patients aged 13 years and older, boys had significantly larger aSMA areas than girls in all three compartments. Among the three compartments, PSMA had the strongest correlation coefficient with height and weight for both boys and girls. CONCLUSIONS: We generated quantile regression curves for three aSMA compartments obtained from cross-sectional CT images and established reference values in children. PSMA values were most strongly correlated with height and weight among the three aSMA compartments.

Development of mortality prediction models for infants with isolated, left-sided congenital diaphragmatic hernia before and after birth.

BACKGROUND: Mortality prediction of congenital diaphragmatic hernia (CDH) is essential for developing treatment strategies, including fetal therapy. Several researchers have reported prognostic factors for this rare but life-threatening condition; however, the optimal combination of prognostic factors remains to be elucidated. OBJECTIVES: This study aimed to develop the most discriminative prenatal and postnatal models to predict the mortality of infants with an isolated left-sided CDH. METHODS: This multi-institutional retrospective cohort study included infants with CDH born at 15 tertiary hospitals of the Japanese CDH Study Group between 2011 and 2016. We developed multivariable logistic models with every possible combination of predictors and identified models with the highest cross-validated area under the receiver operating characteristic curve (AUC) for prenatal and postnatal predictions. RESULTS: Among 302 eligible infants, 44 died before discharge. The prenatal mortality prediction model was based on the observed/expected lung area to head circumference ratio (O/E LHR), liver herniation, and stomach herniation (AUC, 0.830). The postnatal mortality prediction model was based on O/E LHR, liver herniation, and the lowest oxygenation index (AUC, 0.944). CONCLUSION: Our models can facilitate the prenatal and postnatal mortality prediction of infants with isolated left-sided CDH.

A predictive scoring system for small diaphragmatic defects in infants with congenital diaphragmatic hernia.

PURPOSE: To develop a predictive score for small diaphragmatic defects in infants with congenital diaphragmatic hernia (CDH) for determining thoracoscopic surgery indication. METHODS: The Japanese CDH Study Group cohort was randomly divided into derivation (n = 397) and validation (n = 396) datasets. Using logistic regression, a prediction model and weighted scoring system for small diaphragmatic defects were created from derivation dataset and validated with validation dataset. RESULTS: Six weighted variables were selected: no hydramnios, 1 point; 1 min Apgar score of 5-10, 1 point; apex type of the lung (left lung is detected radiographically in apex area), 1 point; oxygenation index < 8, 1 point; abdominal nasogastric tube (tip of the nasogastric tube is detected radiographically in the abdominal area), 2 points; no right-to-left flow of ductus arteriosus, 1 point. In validation dataset, rates of small diaphragmatic defects for Possible (0-3 points), Probable (4-5 points), and Definite (6-7 points) groups were 36%, 81%, and 94%, respectively (p < 0.001). Additionally, sensitivity, specificity, positive predictive value, and C statistics were 0.78, 0.79, 0.88, 0.76, and 0.45, 0.94, 0.94, 0.70 for Probable and Definite groups, respectively. CONCLUSION: Our scoring system effectively predicted small diaphragmatic defects in infants with CDH.

Frequency and function of circulating regulatory T-cells in biliary atresia.

PURPOSE: Although the impairment of regulatory T-cells (Tregs) has been shown in the liver or portal area of biliary atresia (BA) the frequency and function of circulating Tregs in BA patients is poorly understood. We aimed to investigate the frequency and function of circulating Tregs in BA patients. METHODS: Peripheral blood mononuclear cells were collected from 25 BA patients and 24 controls. Treg frequency was measured by flow cytometry; function was determined by T-cell proliferation assay. We also assessed the association between Treg frequency/function and clinical parameters in BA cases. RESULTS: There was no significant difference between the two groups in both frequency (BA: 3.4%; control: 3.2%; p = 0.97) and function (BA: 22.0%; control: 7.5%; p = 0.23) of Tregs. We further focused on 13 preoperative BA patients and 14 age-matched controls. Neither Treg frequency nor function were significantly different (frequency: BA: 4.6%; control: 3.4%; p = 0.38, function: BA: 2.7%; control: 7.6%; p = 0.89). There was no association between Treg frequency/function and clinical parameters. CONCLUSION: Neither the frequency nor function of circulating Tregs was affected in BA patients, suggesting the negative role of circulating Tregs in the pathogenesis of BA. Further investigation of local Treg profiles is warranted.

The efficacy of the postnatal nasogastric tube position as a prognostic marker of left-sided isolated congenital diaphragmatic hernia.

PURPOSE: The prenatal diagnosis of the stomach position in congenital diaphragmatic hernia (CDH) has been a reliable prognostic factor, but few studies have focused on the postnatal position. We therefore evaluated the significance of the nasogastric (NG) tube position just after birth. METHODS: The Japanese CDH Study Group database enrolled 1037 CDH neonates over 15 years. In our multicenter retrospective study, 464 cases of left-sided isolated CDH with prenatal diagnoses were divided into two groups: NG tube below the diaphragm (BD; n = 190) or above the diaphragm (AD; n = 274). The primary outcome was the 90-day survival rate, and the secondary outcomes were mechanical ventilation duration, hospitalization duration, and recurrence rate. RESULTS: The BD group had a significantly higher 90-day survival rate (98.4 vs. 89.4%, p < 0.001), shorter mechanical ventilation (11 vs. 19 days, p < 0.001), shorter hospitalization (38 vs. 59 days, p < 0.001), and lower recurrence rate (p = 0.002) than the AD group. A multivariate analysis showed that BD (adjusted odds ratio, 3.68; 95% confidence interval 1.02-13.30) was a favorable prognostic factor for the 90-day survival. CONCLUSION: The assessment of the NG tube position revealed it to be a reliable prognostic factor of left-sided isolated CDH. Therefore, it should be included as a routine assessment.

Prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia: a systematic review and meta-analysis.

PURPOSE: This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH). METHODS: A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed. RESULTS: A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 [95% confidence interval (CI) 4.65-30.89], 11.14 (95% CI 5.19-23.89), and 10.28 (95% CI 3.38-31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position. CONCLUSIONS: This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH.