Biventricular function in preterm infants with patent ductus arteriosus ligation: A three-dimensional echocardiographic study.

BACKGROUND: The detailed hemodynamics after patent ductus arteriosus (PDA) ligation in preterm infants remain unknown. We aimed to clarify the effect of surgical ligation on left ventricular (LV) and right ventricular (RV) volume and function. METHODS: Echocardiography was performed in 41 preterm infants (median gestational age: 25 weeks) before and after PDA ligation. Global longitudinal strain was determined using three-dimensional speckle-tracking echocardiography. These values were compared with those in 36 preterm infants without PDA (non-PDA). RESULTS: Preoperatively, the PDA group had greater end-diastolic volume (EDV) and cardiac output (CO) in both ventricles, a higher LV ejection fraction (LVEF) (53% vs 44%) and LV global longitudinal strain, and a lower RVEF (47% vs 52%) than the non-PDA group. At 4-8 h postoperatively, the two groups had a similar LVEDV and RVEDV. However, the PDA group had a lower EF and CO in both ventricles than the non-PDA group. At 24-48 h postoperatively, the RVEF was increased, but the LVEF remained decreased, and LVCO was increased. CONCLUSIONS: PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery. Three-dimensional echocardiography may be beneficial to understand the status of both ventricles. IMPACT: Preterm infants are at high risk of hemodynamic compromise following a sudden change in loading conditions after PDA ligation. Three-dimensional echocardiography enables quantitative and serial evaluation of ventricular function and volume in preterm infants with PDA. PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery.

Modeling of multiple atrial septal defects with inferior vena cava rim deficiency: Three-dimensional visualization of the rim based on transthoracic echocardiographic imaging.

The morphologic features of the multiple atrial septal defects assessed by TTE-based 3D imaging were similar to those by 3D-TEE. TTE-based 3D model had excellent visibility, allowing observation of 3D structure of the rims of the defects. It may be useful method for assessment of the multiple atrial septal defects.

Feasibility of Three-Dimensional Echocardiographic Analysis in Newborns by Novice Observers.

Three-dimensional echocardiography (3DE) provides better interobserver agreement than conventional methods. However, more evidence of whether there is good agreement between novice and experienced observers, especially in pediatric 3DE analysis, is required. We conducted 3DE analysis training in novice observers and investigated the agreement when analyzing 3DE images between novice and experienced observers. One experienced and 4 novice observers independently analyzed 60 3DE images obtained from neonates. The left and right ventricular end-diastolic volume (LVEDV and RVEDV), end-systolic volume (LVESV and RVESV), ejection fraction (LVEF and RVEF), left ventricular global longitudinal strain, and global circumferential strain (LVGLS and LVGCS) were calculated. The novices received hands-on instruction in the analysis procedure before the analysis and received further feedback after their first 40 analyses. Agreement between the novices and the experienced observer was evaluated by the intra-class correlation coefficient (ICC) and percentage difference in 3 groups of 20 images each (images 1-20, 21-40, and 41-60). The ICC of LVEDV was > 0.85 from the first 20 images and increased with experience. The ICCs for RVEDV and RVESV were low from the first 20 images but increased linearly, reaching an ICC > 0.9 in 3 of the 4 novice observers in the last 20 images. The range of the percentage difference was small for LVEDV, RVEDV, LVEF, and RVEF. Novices show an experienced level of 3DE analysis capability in LVEDV and RVEDV after analyzing 40 to 60 images. Training of novices is effective for analyzing LVEDV and RVEDV in 3DE images.

Death of children with Down syndrome by gestational age and cause.

BACKGROUND: We often encounter preterm infants with Down syndrome (DS) who die in the neonatal intensive care unit (NICU). In this study, we examined survival until NICU discharge and assessed the developmental prognosis of preterm infants with DS. METHODS: We retrospectively reviewed 416 infants with DS hospitalized during the past 27 years at our NICU. RESULTS: Death occurred in 8/20 (40%) infants at <32 weeks' gestation, 11/23 (48%) at 32-33 weeks, 9/99 (9%) at 34-36 weeks, and 9/274 (3%) at >36 weeks. In total, 84% of infants who died and 25% of those who survived had a non-reassuring fetal status (p < 0.001). Sex, small-for-gestational-age status, and postnatal transport were not associated with death. The main causes of death were bronchopulmonary dysplasia in 4/8 (50%) infants at <32 weeks' gestation, transient abnormal myelopoiesis in 11/20 (55%) and lymphatic dysplasia in 6/20 (30%) at 32-36 weeks, and varied causes at >36 weeks. Among survivors born at <34 weeks' gestation, 6/19 (32%) aged >2 years had moderate or severe cerebral palsy. CONCLUSIONS: These data on the high mortality and morbidity of preterm infants with DS may be useful for patient treatment and parent counseling in NICUs treating critically ill infants. IMPACT: Most infants with Down syndrome born at <34 weeks' gestation are born by cesarean section because of the non-reassuring fetal status. The mortality rate before discharge for infants with Down syndrome born at <34 weeks' gestation was 40%, and 30% of survivors developed moderate or severe cerebral palsy. The risk of death due to bronchopulmonary dysplasia and pulmonary hypertension was high in very preterm infants with Down syndrome despite the absence of chorioamnionitis. Infants with Down syndrome were born 1-2 weeks earlier than unaffected controls.

Right to left ventricular volume ratio is associated with mortality in congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality. We performed this study to test the hypothesis that left ventricular (LV) and right ventricular (RV) volumes assessed by three-dimensional echocardiography may be associated with mortality in CDH. METHODS: This study was a single-center retrospective cohort study involving 35 infants with CDH. RV and LV end-diastolic volume (RVEDV and LVEDV, respectively) were measured by three-dimensional echocardiography and were corrected by birth body weight (BBW) on day 1. RVEDV/BBW, LVEDV/BBW, and LVEDV/RVEDV were compared between CDH survivors and non-survivors. Receiver-operating characteristic curve analysis was performed to assess the predictive ability for mortality of the echocardiographic parameters. RESULTS: Comparing CDH non-survivors (n = 6) with survivors (n = 29), respectively, RVEDV/BBW was significantly larger (2.54 ± 0.33 vs 1.86 ± 0.35 ml/kg; P < 0.01), LVEDV/BBW was significantly smaller (0.86 ± 0.21 vs 1.22 ± 0.33 ml/kg; P < 0.001), and LVEDV/RVEDV was significantly lower (0.34 ± 0.06 vs 0.66 ± 0.18; P < 0.001). The area under the curve for LVEDV/RVEDV was the largest (0.98). CONCLUSIONS: Three-dimensional echocardiographic volume imbalance between the RV and LV was remarkable in CDH non-survivors. The LVEDV/RVEDV ratio may be associated with mortality in CDH. IMPACT: Mortality with congenital diaphragmatic hernia (CDH) is high, and evaluating left and right ventricular structures and functions may be helpful in assessing the prognosis. Three-dimensional (3D) echocardiography indicated that the left ventricular end-diastolic volume/right ventricular end-diastolic volume ratio within 24 h after birth was associated with mortality in CDH infants. The usefulness of this ratio should be validated in prospective multicenter studies involving larger numbers of patients.

Common Blood Test Indices for Predicting Transient Abnormal Myelopoiesis-Related Mortality in Infants with Down Syndrome.

Transient abnormal myelopoiesis (TAM) can cause early death in children with Down syndrome, and liver failure is the most common cause of death. The aim of this single-center retrospective study was to identify a quantitative index for predicting TAM-related mortality at the time of diagnosis. Of the 462 children with Down syndrome admitted to our hospital from 1992 to 2021, we studied 12 infants with TAM-related death and 31 survivors who were diagnosed with TAM. In the death and survival groups, the median gestational ages were 34.9 and 37.1 weeks, respectively (p = 0.12). At diagnosis, the white blood cell (WBC) counts were 99.2 and 36.2 × 109/L (p = 0.011), the hemoglobin concentrations were 131 and 159 g/L (p = 0.009), and the serum albumin concentrations were 23 and 31 g/L (p < 0.001), respectively. The areas under the receiver operating characteristic curve for the abilities of the WBC count, hemoglobin, and serum albumin at diagnosis to predict survival were 0.75, 0.76, and 0.85, respectively. The serum albumin concentration threshold of 28 g/L at diagnosis had sensitivity of 0.79 and specificity of 0.82. Gestational age and serum albumin concentration were entered into a logistic regression model. The serum albumin concentration was an independent indicator of TAM-related death (adjusted odds ratio, 0.78; 95% confidence interval, 0.65-0.93; p = 0.005). In conclusion, a low serum albumin concentration at diagnosis may be a good predictor of TAM-related death.

Genome Analysis in Sick Neonates and Infants: High-yield Phenotypes and Contribution of Small Copy Number Variations.

OBJECTIVE: To delineate the diagnostic efficacy of medical exome, whole exome, and whole genome sequencing according to primary symptoms, the contribution of small copy number variations, and the impact of molecular diagnosis on clinical management. STUDY DESIGN: This was a prospective study of 17 tertiary care centers in Japan, conducted between April 2019 and March 2021. Critically ill neonates and infants less than 6 months of age were recruited in neonatal intensive care units and in outpatient clinics. The patients underwent medical exome, whole exome, or whole genome sequencing as the first tier of testing. Patients with negative results after medical exome or whole exome sequencing subsequently underwent whole genome sequencing. The impact of molecular diagnosis on clinical management was evaluated through contacting primary care physicians. RESULTS: Of the 85 patients, 41 (48%) had positive results. Based on the primary symptoms, patients with metabolic phenotypes had the highest diagnostic yield (67%, 4/6 patients), followed by renal (60%, 3/5 patients), and neurologic phenotypes (58%, 14/24 patients). Among them, 4 patients had pathogenic small copy number variations identified using whole genome sequencing. In the 41 patients with a molecular diagnosis, 20 (49%) had changes in clinical management. CONCLUSIONS: Genome analysis for critically ill neonates and infants had a high diagnostic yield for metabolic, renal, and neurologic phenotypes. Small copy number variations detected using whole genome sequencing contributed to the overall molecular diagnosis in 5% of all the patients. The resulting molecular diagnoses had a significant impact on clinical management.

Altered brain metabolite concentration and delayed neurodevelopment in preterm neonates.

BACKGROUND: A very-low-birth-weight (VLBW) preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes. In this study, we investigated how neonatal brain metabolite concentrations changed with postmenstrual age and examined the relationship between changes in concentration (slopes) and neurodevelopmental level at 3-4 years. METHODS: We retrospectively examined 108 VLBW preterm infants who had brain single-voxel magnetic resonance spectroscopy at 34-42 weeks' postmenstrual age. Neurodevelopment was assessed using a developmental test, and subjects were classified into four groups: developmental quotient <70, 70-84, 85-100, and >100. One-way analyses of covariance and multiple-comparison post hoc tests were used to compare slopes. RESULTS: We observed correlations between postmenstrual age and the concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA) (p < 0.001); creatine and phosphocreatine (p < 0.001); glutamate and glutamine (p < 0.001); and myo-inositol (p = 0.049) in the deep gray matter; and tNAA (p < 0.001) in the centrum semiovale. A significant interaction was noted among the tNAA slopes of the four groups in the deep gray matter (p = 0.022), and we found a significant difference between the <70 and 85-100 groups (post hoc, p = 0.024). CONCLUSIONS: In VLBW preterm infants, the slopes of tNAA concentrations (adjusted for postmenstrual age) were associated with lower developmental quotients at 3-4 years. IMPACT: In very-low-birth-weight preterm-born infants, a slower increase in tNAA brain concentration at term-equivalent age was associated with poorer developmental outcomes at 3-4 years. The increase in tNAA concentration in very-low-birth-weight infants was slower in poorer developmental outcomes, and changes in tNAA concentration appeared to be more critical than changes in tCho for predicting developmental delays. While tNAA/tCho ratios were previously used to examine the correlation with neurodevelopment at 1-2 years, we used brain metabolite concentrations.

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.

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.

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.

Changes in regional oxygen saturation of the kidney and brain of infants during hospitalization.

BACKGROUND: In pre-term infants, the postnatal changes in the regional oxygen saturation (rSO2) of the brain and kidney are unclear. METHODS: We performed a prospective observational study. We measured the cerebral/renal rSO2 ratio and recorded the associated clinical features of infants born at 23 to 41 weeks of gestation weekly from the early postnatal period to discharge. RESULTS: The median cerebral/renal rSO2 ratios (interquartile ranges) between birth and the expected date of birth were 1.13 (1.06-1.26) at 23-24 weeks (n = 7), 1.18 (1.10-1.32) at 25-26 weeks (n = 11), 1.24 (1.11-1.37) at 27-28 weeks (n = 9), 1.12 (1.05-1.19) at 29-30 weeks (n = 4), 1.11 (1.03-1.15) at 31-32 weeks (n = 5), 1.02 (0.98-1.06) at 33-34 weeks (n = 9), 0.98 (0.94-1.06) at 35-36 weeks (n = 19), and 0.95 (0.86-0.99) at 37-41 weeks of gestation (n = 22). The median cerebral/renal rSO2 ratio did not significantly change after birth, but with increasing gestational age, the cerebral/renal rSO2 ratio at the expected date of birth decreased (r = - 0.74, p < 0.001). Nephrotoxic drugs did not affect cerebral/renal rSO2 at the expected date of birth, after adjustment for clinical factors. CONCLUSIONS: Unlike in most infants born after the late pre-term period, the renal rSO2 remained lower than the cerebral rSO2 on the expected date of birth in infants born very pre-term.

Comparison of Predictive Values of Magnetic Resonance Biomarkers Based on Scan Timing in Neonatal Encephalopathy Following Therapeutic Hypothermia.

OBJECTIVE: To determine the optimal quantitative magnetic resonance (MR) biomarker in neonatal encephalopathy following therapeutic hypothermia based on scan timing. STUDY DESIGN: This retrospective study included 98 neonates (35-41 weeks of gestation) with neonatal encephalopathy, who underwent therapeutic hypothermia; diffusion-weighted imaging and proton MR spectroscopy were performed at 24-96 hours (n = 56) and 7-14 days (n = 92) after birth, respectively, to estimate apparent diffusion coefficient (ADC) values, N-acetylaspartate and N-acetylaspartylglutamate (tNAA), lactate, and choline concentrations, and lactate/tNAA, tNAA/choline ratios in the deep gray matter. Adverse outcomes included death or neurodevelopmental impairment at 18-22 months of age. We used receiver operating characteristic curves to examine the prognostic accuracy of each MR biomarker. RESULTS: Deep gray matter tNAA concentrations showed the best prognostic value, with an area under the curve (AUC) of 0.97 and 1.00 at 24-96 hours and 7-14 days after birth, respectively. At 24-96 hours of age, ADC values, lactate concentrations, and lactate/tNAA ratios showed prognostic value with AUCs of 0.90, 0.95, and 0.97, respectively. At 7-14 days of age, the AUCs of ADC values, lactate, and lactate/tNAA ratios were 0.61, 0.67, and 0.80, respectively; these were lower than those at 24-96 hours of age. CONCLUSIONS: During the first 2 weeks of life, the deep gray matter tNAA concentration was the most accurate quantitative MR biomarker. Although ADC values, lactate levels, and lactate/tNAA ratios also showed high prognostic value during 24-96 hours of life, only tNAA retained high prognostic value in the second week of life.

Clinical features of very-low-birthweight infants with congenital heart disease.

BACKGROUND: Few studies have investigated the developmental prognosis of very-low-birthweight (VLBW) infants with congenital heart diseases (CHDs). This study aimed to determine the mortality and morbidity, including the developmental prognosis, of VLBW infants with CHD. METHODS: This single-center, retrospective cohort study included VLBW infants admitted to the neonatal intensive care unit from January 2006 to December 2011. Perinatal records were reviewed for CHD diagnosis, treatment details, comorbidities, mortality, and long-term neurodevelopmental outcomes. The characteristics and neurological developmental quotients at around the age of 3 years were compared among the following three groups of VLBW infants with CHDs: biventricular circulation without intervention (without surgery), biventricular circulation with intervention (catheter intervention or one-stage surgery), and single-ventricular circulation (Fontan-type multiple-stage surgery). RESULTS: Among a total of 449 VLBW infants admitted during this period, 45 (10.0%) infants had CHDs, including 25 infants with congenital abnormalities (chromosomal abnormalities and/or multiple anomalies). All 13 infants who died before discharge had congenital abnormalities. The incidence rates of comorbidities were not higher in VLBW infants with CHDs than in those without CHDs. The developmental quotients of the no-surgery, catheter intervention or one-stage surgery, and Fontan-type multiple-stage surgery groups were 87.2 ± 10.9, 91.3 ± 4.7, and 63.7 ± 8.6, respectively. CONCLUSIONS: The neurological development at around the age of 3 years in VLBW infants with biventricular circulation was in the borderline-to-normal range; however, that in infants with single-ventricular circulation was poor. Further studies are needed to comprehend the neurological development of VLBW infants with CHDs better.

Clinical guidelines for the treatment of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm in which abdominal organs herniate through the defect into the thoracic cavity. The main pathophysiology is respiratory distress and persistent pulmonary hypertension because of pulmonary hypoplasia caused by compression of the elevated organs. Recent progress in prenatal diagnosis and postnatal care has led to an increase in the survival rate of patients with CDH. However, some survivors experience mid- and long-term disabilities and complications requiring treatment and follow-up. In recent years, the establishment of clinical practice guidelines has been promoted in various medical fields to offer optimal medical care, with the goal of improvement of the disease' outcomes, thereby reducing medical costs, etc. Thus, to provide adequate medical care through standardization of treatment and elimination of disparities in clinical management, and to improve the survival rate and mid- and long-term prognosis of patients with CDH, we present here the clinical practice guidelines for postnatal management of CDH. These are based on the principles of evidence-based medicine using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The recommendations are based on evidence and were determined after considering the balance among benefits and harm, patient and society preferences, and medical resources available for postnatal CDH treatment.

Acute respiratory effect of transpyloric feeding for respiratory exacerbation in preterm infants.

OBJECTIVES: Gastroesophageal reflux may exacerbate chronic lung disease in preterm infants. We evaluated the short-term effects of transpyloric feeding on respiratory status in preterm infants during mechanical ventilation. METHODS: We retrospectively collected data from the hospital information management system. To evaluate the effect of transpyloric feeding on oxygenation, we compared changes in SpO2/FiO2 ratios before and after commencing transpyloric feeding by a piecewise linear regression model. RESULTS: We examined 33 infants (median gestational age, 25.4 weeks; median birth weight, 656 g) who underwent transpyloric feeding. All tubes were placed at the bedside without fluoroscopy. No cases of unsuccessful placement, gastroduodenal perforation, or tracheal misinsertion occurred. Transpyloric feeding began at a median age of 18 (interquartile range, 15-23) days. Mean SpO2/FiO2 (±SD) ratios were 391 (±49), 371 (±51), 365 (±56), and 366 (±53) 72-96 h before, 0-24 h before, 48-72 h after, and 96-120 h after starting transpyloric feeding, respectively. The rate of change per hour of SpO2/FiO2 ratios increased 48-120 h after compared with 0-96 h before transpyloric feeding (0.03 [95% confidence interval, -0.10 to 0.17] vs. -0.29 [-0.47 to -0.12]) (p=0.007). No apparent changes occurred in the mean airway pressure, amplitude pressure, or pCO2. CONCLUSIONS: Transpyloric feeding during mechanical ventilation can prevent the deterioration of oxygenation without major complications at the stage of respiratory exacerbation in preterm infants.

Thoracoscopic repair of congenital diaphragmatic hernia in neonates: findings of a multicenter study in Japan.

PURPOSE: We compared the efficacy of thoracoscopic repair (TR) with that of open repair (OR) for neonatal congenital diaphragmatic hernia (CDH). METHODS: The subjects of this multicenter retrospective cohort study were 524 infants with left-sided isolated CDH, diagnosed prenatally, and treated at one of 15 participating hospitals in Japan between 2006 and 2018. The outcomes of infants who underwent TR and those who underwent OR were compared, applying propensity score matching. RESULTS: During the study period, 57 infants underwent TR and 467 underwent OR. Ten of the infants who underwent TR required conversion to OR for technical difficulties and these patients were excluded from the analysis. The survival rate at 180 days was similar in both groups (TR 98%; OR 93%). Recurrence developed after TR in 3 patients and after OR in 15 patients (TR 7%, OR 3%, p = 0.40). The propensity score was calculated using the following factors related to relevance of the surgical procedure: prematurity (p = 0.1), liver up (p < 0.01), stomach position (p < 0.01), and RL shunt (p = 0.045). After propensity score matching, the multivariate analysis adjusted for severity classification and age at surgical treatment revealed a significantly shorter hospital stay (odds ratio 0.50) and a lower incidence of chronic lung disease (odds ratio 0.39) in the TR group than in the OR group. CONCLUSIONS: TR can be performed safely for selected CDH neonates with potentially better outcomes than OR.

Optimal timing of surgery in infants with prenatally diagnosed isolated left-sided congenital diaphragmatic hernia: a multicenter, cohort study in Japan.

PURPOSE: To date, there is no compelling evidence of the optimal timing of surgery for congenital diaphragmatic hernia (CDH). This study aimed to establish the optimal timing of surgery in neonates with isolated left-sided CDH. METHODS: This multicenter cohort study enrolled 276 patients with isolated left-sided CDH at 15 institutions. Based on the timing of surgery, the patients were classified into four groups [< 24 h (G1), 24-47 h (G2), 48-71 h (G3), and ≥ 72 h (G4)]. The clinical outcomes were compared among the groups using a logistic regression model, after adjusting for potential confounders, such as disease severity. RESULTS: Multivariate analyses showed that G2 also had a lower mortality rate than the other groups. In mild and severe cases, there were no significant differences in mortality across the four groups. In moderate cases, G2 resulted in significantly increased survival rates, compared with G1. CONCLUSION: The study results suggest that surgery within 24 h of birth is not recommended for patients with moderate severity CDH, that there is no benefit in the delay of surgery for more than 72 h in mild severity CDH patients, and that there is no definite optimal time to perform surgery in severe cases of CDH.

Best pre-ductal PaO2 prior to extracorporeal membrane oxygenation as predictor of mortality in patients with congenital diaphragmatic hernia: a retrospective analysis of a Japanese database.

PURPOSE: Predicting lethal pulmonary hypoplasia in infants with congenital diaphragmatic hernia (CDH) before extracorporeal membrane oxygenation (ECMO) initiation is difficult. This study aimed to predict lethal pulmonary hypoplasia in patients with CDH prior to ECMO. METHODS: This was a multicenter cohort study involving neonates prenatally diagnosed with isolated unilateral CDH (born 2006-2020). Patients who required ECMO due to respiratory insufficiency were included in this study. Patients who underwent ECMO due to transient disorders were excluded from analysis. Blood gas analysis data within 24 h of birth were compared between survivors and non-survivors. Predictive abilities were assessed for factors with significant differences. RESULTS: Overall, 34 patients were included (18 survivors and 16 non-survivors). The best pre-ductal PaO2 was significantly lower in non-survivors than in survivors (50.4 [IQR 30.3-64.5] vs. 67.5 [IQR 52.4-103.2] mmHg, respectively; p = 0.047). A cutoff PaO2 of 42.9 mmHg had a sensitivity, specificity, and positive predictive value of 50.0%, 94.4%, and 88.9%, respectively, to predict mortality. CONCLUSION: The best PaO2 within 24 h after birth predicted mortality following ECMO initiation. This should be shared to families and caregivers to optimize the best interests of the infants with CDH.

Using airway resistance measurement to determine when to switch ventilator modes in congenital diaphragmatic hernia: a case report.

BACKGROUND: Congenital diaphragmatic hernia is a deficiency of the fetal diaphragm resulting in herniation of the abdominal viscera into the thoracic cavity. The best method of respiratory management of congenital diaphragmatic hernia is unclear, but high frequency oscillatory ventilation is often used as the initial ventilator mode for severe congenital diaphragmatic hernia. When it becomes impossible to maintain the pre-ductal saturations, the timing of successful switching of the ventilation mode from high frequency oscillatory ventilation to conventional mechanical ventilation remains unclear. Herein, we reported two cases in which airway resistance measurements based on pulmonary function tests were used for making the decision to switch the ventilator mode from high frequency oscillatory ventilation to conventional mechanical ventilation in patients with left isolated congenital diaphragmatic hernia. CASE PRESENTATION: Two 0-day-old infants with congenital diaphragmatic hernia were admitted to our hospital. In both patients, high frequency oscillatory ventilation was started initially, and the levels of saturation gradually rose within a few hours after birth. After 24 h of high frequency oscillatory ventilation, the level of saturation decreased, and the dissociation of pre-ductal and post-ductal saturation re-occurred. The respiratory-system resistance was 515 and 403 cmH2O·kg/L/s, respectively. Because the respiratory-system resistance was elevated, we decided to change the ventilator mode from high frequency oscillatory ventilation to conventional mechanical ventilation. After switching to conventional mechanical ventilation, the patients' heart rate and saturation increased immediately. CONCLUSIONS: In patients with congenital diaphragmatic hernia, resistance levels of > 400 cmH2O·kg/L/s may indicate high airway resistance and suggest greater alveolar vibration attenuation. When respiratory-system resistance reaches over 400 cmH2O·kg/L/s, it may be an optimal time for switching from high frequency oscillatory ventilation to conventional mechanical ventilation.