Fetal Lung Volume Research Articles

Timing of Prenatal Magnetic Resonance Imaging in the Assessment of Congenital Diaphragmatic Hernia

Introduction: Fetal magnetic resonance imaging (MRI) has been used to stratify severity of congenital diaphragmatic hernia (CDH) after ultrasound diagnosis. The purpose of this study was to determine if timing of MRI influenced prediction of severity of outcome in CDH. Methods: A single institution retrospective review of all CDH referred to our institution from February 2004 to May 2017 was performed. Patients were included if they underwent at least 2 fetal MRIs prior to delivery. Prenatal MRI indices including observed-to-expected total fetal lung volume (o/e TFLV) were evaluated. Indices were categorized by trimester, either 2nd (20–27 weeks gestation) or 3rd trimester (>28 weeks gestation) and further analyzed for outcome predictability. Primary outcomes were survival, extracorporeal membrane oxygenation (ECMO), and pulmonary hypertension (PAH). Student t test and logistic and linear regression were used for data analyses. Results: Of 256 fetuses evaluated for CDH, 197 were further characterized by MRI with 57 having both an MRI in the 2nd and 3rd trimesters. There was an average of 9.95 weeks (±4.3) between the 1st and 2nd MRI. Second trimester o/e TFLV was the only independent predictor of survival by logistic regression (OR 0.890, p < 0.01). Third trimester MRI derived lung volumes were associated with, and independent predictors of, severity of PAH and need for ECMO. Interval TFLV growth was a strong predictor of PAH postnatally (OR 0.361, p < 0.01). Overall cohort survival was 79%. Conclusion: Accuracy of MRI lung volumes to predict outcomes is dependent on the ­gestational age at the time of exam. While MRI lung volumes at either the 2nd or 3rd trimester are predictive of morbidity, 2nd trimester lung volumes strongly correlated with mortality.

A multifactorial severity score for left congenital diaphragmatic hernia in a high-risk population using fetal magnetic resonance imaging.

Adverse outcomes for infants born with left congenital diaphragmatic hernia (CDH) have been correlated with fetal imaging findings. We sought to corroborate these correlations in a high-risk cohort and describe a predictive mortality algorithm combining multiple imaging biomarkers for use in prenatal counseling. We reviewed fetal MRI examinations at our institution from 2004 to 2016 demonstrating left-side CDH. MRI findings, hospital course and outcomes were recorded and analyzed using bivariate and multivariable analysis. We generated a receiver operating curve (ROC) to determine a cut-off relation for mortality. Finally, we created a predictive mortality calculator. Of 41 fetuses included in this high-risk cohort, 41% survived. Per bivariate analysis, observed-to-expected total fetal lung volume (P=0.007), intrathoracic position of the stomach (P=0.049), and extracorporeal membrane oxygenation (ECMO) requirement (P<0.001) were significantly associated with infant mortality. Youden J statistic optimized the ROC for mortality at 24% observed-to-expected total fetal lung volume (sensitivity 64%, specificity 82%, area under the curve 0.72). On multivariable analysis, observed-to-expected total fetal lung volume ± 24% was predictive of mortality (adjusted odds ratio, 95% confidence interval: 0.09 [0.02, 0.55]; P=0.008). We derived a novel mortality prediction calculator from this analysis. In this high-risk cohort, decreased observed-to-expected total fetal lung volume and stomach herniation were significantly associated with mortality. The novel predictive mortality calculator utilizes information from fetal MR imaging and provides prognostic information for health care providers. Creation of similar predictive tools by other institutions, using their distinct populations, might prove useful in family counseling, especially where there are discordant imaging findings.

Optimization of Prenatal Screening for Developmental Lung Anomalies

Objective: to determine the list of ultrasound criteria for normal development of the fetal lung, the use of which will make it possible to identify lung malformations in the fetus effectively, as well as to predict the development of lung hypoplasia in the newborn. Material of the research. The fetuses of singleton pregnancy in 1570 female patients of Minsk during the gestation period of 20-37 weeks. Results. The minimum list of the ultrasound criteria for the features of the lung development, which should be used for screening ultrasound examinations of pregnant women aimed at the detection of congenital lung malformations of the fetus, has been determined. The work indicates cases which require additional measurement of the lung volume of the fetus, the most optimal method for which is to use the VOCAL software package during three-dimensional sonography or direct measurement by MRI. The measurement data for the percentile values of the fetal lung volume taking into account the regional biometric features, as well as the percentile measurement data for the quantity of amniotic fluid have been determined. Conclusion. The minimum list of the ultrasound criteria for adequate lung development, the use of which during the screening ultrasound examinations of pregnant women will make it possible to detect congenital lung malformations of the fetus with high sensitivity, includes such characteristics as parenchyma homogeneity, diaphragm position, fluid in the pleural cavity, and the presence of fluid movement through the airways. The prenatal prediction of the development of respiratory distress syndrome in newborns requires direct measurement of the lung volume by means of the volumetric calculation program of three-dimensional sonography or MRI, followed by the assessment of the results using the tables of the regional percentile values, developed by the authors. Also, in cases of oligohydramnios, to make such a prediction, it is necessary to assess the quantity of amniotic fluid using the tables of the regional percentile values, developed by the authors.

Prenatal prediction of survival in congenital diaphragmatic hernia: An audit of postnatal outcomes

PurposeEffective antenatal counseling in congenital diaphragmatic hernia (CDH) relies on proper measurement of prognostic indices. This quality initiative audited the accuracy of prenatal imaging with postnatal outcomes at two tertiary pediatric referral centers. MethodsPrenatal lung–head ratio (LHR) and total fetal lung volume (TFLV) for CDH patients treated between 2006 and 2017 were retrieved. Study inclusion required at least one LHR or TFLV measurement between 24 and 32 weeks gestational age. Postnatal outcomes [mortality, extracorporeal life support (ECLS) need, patch repair, persistent pulmonary hypertension, oxygen requirement at 28 days] were abstracted from the Canadian Pediatric Surgery Network (CAPSNet) database and local chart review. Univariate and descriptive analyses were conducted. ResultsEighty-two of 121 eligible CDH patients (68%) were included. Overall mortality, ECLS rates, and patch repair were 33%, 12.5%, and 45%, respectively. Lower LHR values correlated with increased rates of each outcome and persisted despite multiple measurements. Values obtained were higher than those in published schemata. LHR values >45% were most associated with survival, avoidance of ECLS, and primary repair. TFLV values only correlated with mortality and patch repair. ConclusionsThis audit confirms that LHR and TFLV values predict CDH outcomes. However, absolute values obtained require careful interpretation and internal review. Level of evidenceIV.

Antenatal management and outcomes of pregnancies with congenital diaphragmatic hernia

The objective of this study is to evaluate the obstetric outcomes of pregnancies with congenital diaphragmatic hernia (CDH). Fifty one pregnancies prenatally diagnosed with CDH at our institution between January 1, 2002 and August 31, 2018 were retrospectively evaluated. The pregnancies were divided into two groups according to neonatal survival. Demographic features, clinical characteristics and prognostic factors were compared between the neonatal survival (n = 16) and non-survival (n = 28) groups. Cut-off values of fetal lung area to head circumference ratio (LHR), observed/expected LHR (o/e LHR) and observed/expected total fetal lung volume (o/e TFLV) for neonatal survival were calculated. Thirty six (70.6%) and fifteen (29.4%) fetuses had left and right sided CDH respectively. Seven patients chose termination of their pregnancies (13.7%). Statistically significant differences were found between survival and non-survival groups in terms of parity, median gestational week at diagnosis, polyhydroamniosis rate, CDH type, stomach position, liver position, median LHR, o/e LHR, o/e TFLV, median 5th minute Apgar score and neonatal operation rate values (p values were 0.03,<0.001, 0.02, 0.006,<0.001, 0.006,<0.001,<0.001,<0.001, 0.04 and <0.001 respectively). According to ROC curve analysis, 1.05 (82% sensitivity, 74% specificity) for LHR, 22.5 (78.6% sensitivity, 73.9% specifity) for o/e LHR and 23.5 (85.7% sensitivity,74.2% specificity) for o/e TFLV were determined to be cut-offs for neonatal survival, respectively, with highest sensitivity and specificity. Earlier gestational week at diagnosis, right sided CDH, presence of liver herniation, supradiaphragmatic stomach position, lower LHR, o/e LHR and o/e TFLV were associated with decreased rates of neonatal survival.

Diagnostic value of MRI-measured fetal percent predicted lung volume for prognosis of left congenital diaphragmatic hernia

Objective To evaluate the diagnostic value of MRI-measured fetal percent predicted lung volume (PPLV) for the prognosis of left congenital diaphragmatic hernia (CDH) in fetus. Methods Clinical data of 32 children who were admitted to Women and Children's Medical Center of Guangzhou from September 2012 to December 2017 for prenatally diagnosed left CDH were retrospectively analyzed. These children were divided into two groups, the survival group (n=24) and the death group (n=8), according to the postoperative outcomes at 30 days after CDH repair. Moreover, they were also divided into non-pulmonary hypertension (non-PH) group (n=20) and PH group (n=12), based on whether they suffered from PH or not. Clinical data such as gestational age, birth weight, Apgar score and PPLV values in different groups were compared with t- or Fisher's exact test. The receiver operating characteristic (ROC) curve of the MRI-measured fetal PPLV values of the 32 children was plotted. Results (1) Comparing with the death group, fetal PPLV was significantly higher [(39.5±2.5)% vs (20.4±2.1)%, t=4.27], the gestations on initial diagnosis of CDH was later [(31.6±4.2) vs (25.4±4.6) gestational weeks, t=3.40], Apgar score of the neonates at 5 min was higher (8.7±1.5 vs 5.7±3.8, t=3.26), and fewer cases of PH were reported in the survival group [16.7% (4/24) and 8/8], all P<0.01. The area under the ROC curve of PPLV values for mortality prediction was 0.930 (95%CI: 0.843-1.016, P<0.01). When the PPLV value was 28.55%, its sensitivity and specificity for death prediction in children with left CDH were 100% and 79%, respectively. (2) Comparing with the PH group, fetal PPLV was significantly higher [(41.7±2.6)% vs (23.0±2.0)%, t=4.98], the gestations on initial diagnosis of CDH was later [(32.3±3.4) vs (26.3±5.2) gestational weeks, t=3.81], neonatal Apgar score at 5 min was higher (8.6±1.4 vs 6.8±2.5, t=2.62) and death rate was lower [0(0/20) vs 8/12] in the non-PH group (all P<0.01). The area under the ROC curve of the PPLV values for predicting PH was 0.902 1 (95%CI: 0.800-1.004, P<0.01). When the PPLV value was 33.67%, its sensitivity and specificity for PH prediction was 100% and 75%, respectively. Conclusions Prenatal MRI measurement of PPLV can be used to predict death or as a warning sign of PH in children with left CDH, which may provide evidence for prenatal evaluation and rational clinical decision-making. Key words: Hernias, diaphragmatic, congenital; Lung volume measurements; Magnetic resonance imaging; Prenatal diagnosis

Fetal brain morphometry on prenatal magnetic resonance imaging in congenital diaphragmatic hernia

Many infants with congenital diaphragmatic hernia (CDH) show brain abnormality on postnatal brain MRI related to severity of CDH, degree of lung hypoplasia, intrathoracic liver, right diaphragmatic hernia and large diaphragmatic defect. It is not known whether these factors affect brain growth in utero in CDH. To assess prenatal brain morphometry and abnormalities on fetal MR in congenital diaphragmatic hernia. We retrospectively reviewed 109 fetal MRIs in 63 fetuses with CDH from 2009 to 2014 (27 died before discharge, 36 survived to discharge). We compared brain injury and gestational-age-corrected z-scores of brain measurements between survivors and non-survivors. We assessed correlations between brain abnormalities and CDH severity. Enlarged extraaxial space was the most common abnormality, frequently seen on fetal MRI at >28weeks of gestation, similar in survivors versus non-survivors. Anteroposterior cerebellar vermis dimension at >28weeks of gestation was smaller in non-survivors compared to survivors (P=.02) and positively correlated with observed/expected total fetal lung volume (P=.01). Transverse cerebellar diameter at >28weeks of gestation was also positively correlated with observed/expected total fetal lung volume (P=.04). We did not identify maturational delay, abnormal parenchymal signal or intracranial hemorrhage on fetal MRI. Enlarged extraaxial spaces in the third trimester was the most common abnormality on fetal MRI in congenital diaphragmatic hernia. Cerebellar dimensions on fetal MRI are associated with CDH severity. There was no major brain parenchymal injury on fetal MRI, even in the third trimester, in CDH survivors and non-survivors.

Early Postnatal Ventricular Dysfunction Is Associated with Disease Severity in Patients with Congenital Diaphragmatic Hernia

To assess patterns of postnatal ventricular function and their relationship to prenatal and postnatal markers of disease severity in infants with congenital diaphragmatic hernia (CDH). In this observational case-control study of cardiac function in infants with CDH in the first 5 days of life, systolic and diastolic function in the right ventricle (RV) and left ventricle (LV) were assessed using speckle tracking echocardiography-derived global strain and tissue Doppler imaging. Correlation between cardiac function and prenatal observed:expected total fetal lung volume (TFLV), oxygenation index (OI), duration of intubation, and hospital length of stay were assessed. All measures of systolic and diastolic function were significantly reduced in the CDH group (n = 25) compared with controls (n = 20) at <48 hours, and were improved by 72-120 hours. LV global systolic longitudinal strain (GLS) correlated with prenatal TFLV (R2 = 0.32; P = .03), OI (R2 = 0.35; P < .001), duration of intubation (R2 = 0.24; P = .04), and length of stay (R2 = 0.4; P = .006). Mean (SD) LV GLS at <48 hours was significantly lower in infants with CDH who did not survive and/or required ECMO compared with those who did not: -11.5 (5.3)% vs -16.9 (5.3)% (P = .02). RV and LV function are impaired in the transitional period in infants with CDH. Early LV systolic function correlates with prenatal and postnatal markers of clinical disease severity and may be an important determinant of disease severity and therapeutic target in CDH. These findings support regular assessment of cardiac function in CDH and investigational trials of targeted cardiovascular therapies.

Fetal Lung Volumes by MRI: Normal Weekly Values From 18 Through 38 Weeks' Gestation.

The purpose of this study is to establish normal total fetal lung volume reference ranges from 18 to 38 weeks' gestation at 1-week intervals. A retrospective analysis of 665 patients who underwent fetal MRI at two tertiary fetal centers from 2001 to 2013 was performed. Total fetal lung volume was measured in at least two planes, either manually or using a 3D workstation. The mean, median, SD, minimum, maximum, and lower and upper quartiles for total fetal lung volume were determined per gestational week. A t test was used to compare our values to previously reported values. A new formula to calculate total fetal lung volume derived from our data was created using a regression model. Comparisons between total fetal lung volume obtained by different imaging planes and manual versus semiautomatic calculation were also performed. The mean normal total fetal lung volume showed a weekly increase from 18 through 35 weeks' gestation. Means were compared with the expected total fetal lung volume generated by the Rypens formula, showing statistically significant lower mean total fetal lung volume from week 19 to week 22 (p < 0.05). Comparison between our data-derived total fetal lung volume formula and the Rypens formula showed very similar values at every gestational age. No difference in total fetal lung volume was seen when comparing imaging planes or manual versus semiautomatic methods. Measured mean total fetal lung volume values at 19-22 weeks are significantly lower than those predicted by the Rypens formula. Therefore, we propose preferential use of our values for prenatal counseling and delivery planning.

Isolated impact of liver herniation on outcome in fetuses with congenital diaphragmatic hernia – A matched-pair analysis based on fetal MRI relative lung volume

PurposeTo evaluate liver-herniation as individual parameter on outcome in children with congenital diaphragmatic hernia. Materials and MethodsIn a retrospective matched-pair analysis based on observed to expected fetal lung volume (o/e FLV), birth weight, gestational age at time-point of examination, status of tracheal occlusion therapy and side of the defect the individual impact of liver-herniation on survival, need for extracorporeal membrane oxygenation (ECMO) therapy and chronic lung disease (CLD) was investigated. In total 61 pairs (122 patients) were included. Fisher’s exact test was used to evaluate influence of liver-herniation and a p-value of <0.05 was defined as statistically significant. The study was approved by the local review board. ResultsChildren with liver-herniation have lower survival rates (78.7% vs. 95.1%; p = 0.0073), need ECMO-therapy more often (41.0% vs. 16.4%; p = 0.0027) and are more likely to develop CLD (71.7% vs. 37.9%; p = 0.0004) than their corresponding matched-pair without liver-herniation. ConclusionLiver-herniation itself and not further lung-volume restriction due to liver-herniation is responsible for poor outcome in CDH.

Neurodevelopmental outcomes in CDH survivors: A single institution's experience

PurposeSurvivors of congenital diaphragmatic hernia (CDH) face high morbidity. We studied the neurodevelopmental outcomes of CDH survivors at a single institution. MethodsCDH survivors born July 2006–March 2016 at a free-standing children's hospital were reviewed. Neurodevelopment was assessed using the Peabody Developmental Motor Scales (PDMS-2) broken into gross, fine, and total motor quotients. Data collected included prenatal variables (liver herniation, defect laterality, observed:expected total fetal lung volume (o:eTFLV) on MRI), birth demographics (sex, race, estimated gestational age (EGA), birth weight (BtWt), 5 min APGAR, associated anomalies), and therapies/hospital course (HFOV/HFJV, ECMO, timing of repair, pulmonary hypertension (PHTN) severity, length of stay, ventilator days). Variables were analyzed using mixed linear modeling. ResultsSixty-eight children were included. Most patients had left-sided CDH (55/68, 81%) without liver herniation (42/68, 62%). ECMO utilization was 25/68 (37%). The mean [95% confidence interval] gross motor quotient for the entire cohort was 87 [84–91], fine motor quotient was 92 [88–96], and total motor quotient was 88 [84–93], representing below average, average, and below average functioning, respectively. o:eTFLV predicted fine motor quotient among prenatal variables. Associated anomalies and ECMO use predicted all quotients in the final model. ConclusionsAssociated anomalies and ECMO use predict neurodevelopmental delay in CDH survivors. Type of StudyRetrospective observational study; Prognostic. Level of EvidenceII.

Predictive value of oxygenation index for outcomes in left-sided congenital diaphragmatic hernia

Background & objectivesCongenital Diaphragmatic Hernia (CDH) is associated with significant morbidity and mortality. This study compares the efficacy of the highest oxygenation index in the first 48 h (HiOI) versus current prenatal indices to predict survival and morbidity. MethodsMedical records of 50 prenatally diagnosed, isolated, left-sided CDH patients treated from January 2011 to April 2016 were reviewed. Data abstracted included HiOI, lung to head ratio (LHR), observed to expected total fetal lung volume (O/E TFLV), percent liver herniation (%LH), 6 month survival, respiratory support at discharge, ventilator days and length of stay. Data were analyzed using parametric and nonparametric tests and regression analyses as appropriate. ResultsHiOI was associated with significantly increased LOS (p<0.001), respiratory support at discharge (p<0.001), greater ventilator days (p=0.001) and higher odds of death (p=0.004) with risk of death increasing by 5% for every one-unit increase in OI. HiOI was statistically a better predictor of LOS than O/E TFLV (p=0.007) and %LH (p=0.02). ConclusionsIn isolated, left-sided CDH patients, HiOI is associated with higher mortality, greater length of stay, more ventilator days and increased respiratory support at discharge. HiOI is a better predictor of length of stay than O/E TFLV and %LH. Type of studyRetrospective Study Level of evidenceII

Combined measurement of fetal lung volume and pulmonary artery resistance index is more accurate for prediction of neonatal respiratory distress syndrome in preterm fetuses: a pilot study

Objective: The objective of this study is to estimate optimal cut-off values for mean fetal lung volume (FLV) and pulmonary artery resistance index (PA-RI) as non-invasive measures to predict neonatal respiratory distress syndrome (RDS) in preterm fetuses.Methods: A prospective study conducted at Ain Shams University Maternity Hospital, Egypt from May 2015 to July 2017: 80 eligible women diagnosed with preterm labor were recruited at 32–36 weeks’ gestation. Before delivery, three-dimensional ultrasound was used to estimate FLV using virtual organ computer-aided analysis (VOCAL), while PA-RI was measured by Doppler ultrasonography.Results: A total of 80 women were examined. Thirty-seven (46%) of the newborns developed neonatal RDS. FLV was significantly lower in neonates who developed RDS (p = .04), whereas PARI was significantly higher in those who did not (p = .02). Cut-off values of FLV ≤27.2 cm3 and PARI ≥0.77 predicted the subsequent development of RDS. Combining both cut-offs generated a more sensitive and specific methodical approach for the prediction of RDS (sensitivity 100%, specificity 88.5%).Conclusion: Measurement of FLV or PA-RI can predict RDS in preterm fetuses. Combined use of both measures bolstered their predictive significance.

The role of three-dimensional ultrasonography fetal lung volume measurement in the prediction of neonatal respiratory function outcome

Background: Respiratory distress is commonly encountered among premature babies immediately after birth resulting in significant neonatal morbidity or mortality. Objectives: To evaluate the possible correlation between three dimensional fetal lung volumes (FLVs) and neonatal respiratory outcomes. Study design: A cohort study included 100 pregnant women who participated in the study and were divided into two groups; group A (n: 50 – women pregnant ±34–37 weeks) and group B (n: 50 – women pregnant ±37+1 to 40 weeks). A three dimensional measurement of the right fetal lung was made using virtual organ computer-aided analysis (VOCAL) software then correlated to neonatal respiratory functions namely Apgar score at birth and the occurrence of respiratory distress syndrome (RDS). Results: In group A, FLV was negatively correlated with Apgar score and the occurrence of RDS. In group B, FLV showed no statistical correlation with Apgar score and the occurrence of RDS. Conclusions: Three dimensional fetal lung volumes might be an accurate noninvasive predictor for the development of RDS among preterm fetuses.

OP05.10: Fetal magnetic resonance imaging (MRI) versus 3D ultrasonography (3D‐US) in assessment of fetal lung volumes in cases at risk of pulmonary hypoplasia

To analyse the correlation and agreement between 3D-US & MRI in measuring fetal lung volumes in cases at risk of developing pulmonary hypoplasia. 38 fetuses at high risk of developing lung hypoplasia either due to extrathoracic causes like renal anomalies causing oligohydraminos and skeletal dysplasias with narrow chest (22cases) or due to intrathoracic causes like congenital cystic adenomatoid malformation (CCAM) and congenital diaphragmatic hernia (CDH) (16 cases) were involved in a cross sectional study. 3D volume data sets of the fetal lungs were acquired were using a commercially available ultrasound system & total lung volumes were calculated using the virtual organ computer-aided analysis (VOCAL) method. MRI obtained fast T2 weighted images of fetal chest in axial, coronal and sagittal planes with assessment of signal intensity & lung volumetry. Comparison between mean lung volumes was performed using unpaired t test. Agreement between the 3D-US and MRI methods was done using Cohen Kappa test. Finally sensitivity, specificity, positive predictive value, negative predictive value & diagnostic accuracy were calculated for 3D-US and for MRI. Good agreement was detected between the two methods(Kappa = 0.715, p = 0.001). The measured lung volumes by 3D-US were smaller than those measured by MRI (p >0.05, non-significant). MRI showed greater specificity, positive predictive value and diagnostic accuracy (100%each) than 3D-US (68.75,78.26 &82.86%) respectively. There is good concordance between 3D-US and MRI in measuring lung volumes and in assessment of pulmonary hypoplasia. MRI can be used complementary to US in borderline cases of pulmonary hypoplasia and in difficult diagnostic situations due to complicated lesions or due to technical problems as in cases of severe oligohydraminos & improper fetal position.

MRI-Based Ratio of Fetal Lung to Body Volume as New Prognostic Marker for Chronic Lung Disease in Patients with Congenital Diaphragmatic Hernia

Background Our aim was to evaluate the prognostic value of magnetic resonance imaging (MRI)-based ratio of fetal lung volume (FLV) to fetal body volume (FBV) as a marker for development of chronic lung disease (CLD) in fetuses with congenital diaphragmatic hernia (CDH). Patients and Methods FLV and FBV were measured and the individual FLV/FBV ratio was calculated in 132 fetuses. Diagnosis of CLD was established following prespecified criteria and graded into mild/moderate/severe if present. Logistic regression analysis was used to calculate the probability of postnatal development of CLD in dependence of the FLV/FBV ratio. Receiver operating characteristic curves were analysed by calculating the area under the curve to evaluate the prognostic accuracy of this marker. Results 61 of 132 fetuses developed CLD (46.21%). The FLV/FBV ratio was significantly lower in fetuses with CLD (p=0.0008; AUC 0.743). Development of CLD was significantly associated with thoracic herniation of liver parenchyma (p<0.0001), requirement of extracorporal membrane oxygenation (ECMO) (p<0.0001) and gestational age at delivery (p=0.0052). Conclusion The MRI-based ratio of FLV to FBV is a highly valuable prenatal parameter for development of CLD. The ratio is helpful for early therapeutic decisions by estimating the probability to develop CLD. Perinatally, gestational age at delivery and ECMO requirement are useful additional parameters to further improve prediction of CLD.

Right Congenital Diaphragmatic Hernias: Is There a Correlation between Prenatal Lung Volume and Postnatal Survival, as in Isolated Left Diaphragmatic Hernias?

Objectives: Whereas left-sided congenital diaphragmatic hernias (L-CDH) have been extensively studied and their prognostic parameters delineated, right-sided hernias (R-CDH) have not. Published results remain inconclusive. The aim of this study is to evaluate if proven prognostic indicators of postnatal survival in the fetus with L-CDH apply to the fetus with R-CDH. Methods: Retrospective single-center study of R-CDH fetuses with available prenatal studies assessed for fetal lung volume by means of ultrasound-measured observed versus expected (O/E) lung area to head circumference (LHR) and magnetic resonance-calculated O/E total lung volume (TLV) in a 12-year time period. Percentage of herniated liver volume and postnatal use of extracorporeal membrane oxygenation (ECMO) were also evaluated. Results: In a cohort of 24 patients, O/E LHR, O/E TLV, percentage of herniated liver, and postnatal use of ECMO are not prognostic indicators of survival in the fetus with R-CDH. Cut-off values of O/E LHR of ≤45 or O/E TLV ≤25, known to select a population of severe cases for the L-CDH fetus, do not appear to extrapolate to the R-CDH fetus, as survival in both R-CDH groups is 60%. Conclusion: The findings in this study suggest that L- and R-CDH appear to behave differently, and that factors that make L-CDH fatal (low O/E TLV and O/E LHR, high-volume herniated liver) may not apply to the fetus with R-CDH.

Observed-to-expected MRI fetal lung volume can predict long-term lung morbidity in infants with congenital diaphragmatic hernia

Objective: Congenital diaphragmatic hernia (CDH) causes pulmonary hypoplasia and pulmonary hypertension, which are associated with long-term respiratory problems in infants. The aim of this study was to establish a marker for predicting lung function at 1 year of age in infants with CDH.Materials and methods: Infants with isolated CDH who were delivered after 35 weeks of gestation from April 2008 to June 2016 at Nagoya University Hospital were registered. Regarding alive infants with CDH, only those who underwent follow-up for at least 1 year were registered. Finally, 48 infants were analyzed in this study.Results: Gestational age at diagnosis, amniotic lamellar body count at birth, observed-to-expected MRI fetal lung volume (percent FLV), liver herniation, and polyhydramnios were found to be significant parameters for predicting mortality in infants with CDH. Regarding alive infants with CDH, percent FLV was the only significant parameter to predict need for oxygen therapy at 1 year of age (p < .05). There was a significant negative correlation between percent FLV and duration of oxygen therapy in infants with CDH (r = .516, p < .001).Conclusions: Percent FLV is a useful predictor of long-term lung morbidity in infants with CDH.

A novel translational model for fetoscopic intratracheal delivery of nanoparticles in piglets

The aim of this study was to assess the feasibility of fetal tracheal injection in the late-gestational pig to target the airways. Following laparotomy and hysterotomy, fetoscopy was performed in pregnant sows to access the fetal trachea. Two volumes of fluospheres were injected (1 and 3 mL). Fluosphere distribution to the different lung lobes was investigated by microscopy. Possible fetal airway injury, caused by the surgical procedure or intratracheal injection, was investigated. Lung morphology and fetal lung volumes were calculated by micro computed tomography (μCT). Intratracheal administration was successfully performed in 20/21 fetuses. Analysis by confocal microscopy demonstrated that 3 mL, and not 1 mL, most efficiently targeted all lung lobes. On high-resolution μCT, total airway volume was estimated at 2.9 mL; strengthening that 3 mL is appropriate to target all lung lobes. No procedural damage was evidenced in the lungs or trachea. Intratracheal injection of nanoparticles is feasible in the pregnant pig and does not cause procedural lung damage. Using an injection volume of 3 mL, all lung lobes were efficiently targeted. This nanoparticle delivery model to fetal airways opens perspectives for therapeutic interventions. © 2016 John Wiley & Sons, Ltd.

Separate Evaluation of the Ipsilateral and Contralateral MR Fetal Lung Volume in Patients With Congenital Diaphragmatic Hernia.

Our study had two objectives. First, we separately evaluated observed-to-expected MR fetal lung volume (FLV) of lungs ipsilateral and contralateral to a congenital diaphragmatic hernia (CDH). Second, we compared the prognostic value of observed-to-expected MR FLV of the ipsilateral and contralateral lungs with that of observed-to-expected MR FLV of both lungs with respect to survival, need for extracorporeal membrane oxygenation (ECMO), and development of chronic lung disease (CLD). We evaluated observed-to-expected MR FLV of the lung ipsilateral to the diaphragmatic defect as well as in the contralateral lung in 107 fetuses with isolated CDH. ROC analysis and logistic regression analysis were performed to assess the prognostic value of the observed-to-expected MR FLV for association with outcome. In all fetuses with CDH, values in the ipsilateral (mean observed-to-expected MR FLV ± SD, 9.4% ± 9.6%) and the contralateral lung (mean observed-to-expected MR FLV, 48.9% ± 18.5%; p < 0.0001) were significantly lower than values measured in healthy fetuses. Observed-to-expected MR FLV of both lungs and of the contralateral and ipsilateral lung revealed significant differences regarding survival (p < 0.0001, p < 0.0001, and p = 0.0170, respectively), need for ECMO (p < 0.0001, p < 0.0001, and p = 0.0051, respectively), and development of CLD (p = 0.0004, p = 0.0002, and p = 0.0460, respectively). Compared with the observed-to-expected MR FLV of both lungs, the observed-to-expected MR FLV of the contralateral lung showed a slightly higher prognostic accuracy regarding survival (AUC = 0.859 vs 0.825) and development of CLD (AUC = 0.734 vs 0.732) and a similar prognostic accuracy regarding need for ECMO (AUC = 0.805 vs 0.826). Observed-to-expected MR FLV of the ipsilateral lung did not show good prognostic value regarding survival (AUC = 0.617), need for ECMO (AUC = 0.673), and development of CLD (AUC = 0.636). These AUCs were significantly smaller than the AUCs resulting from the observed-to-expected MR FLV of both lungs (each p < 0.05) and considerably smaller than the AUCs of the observed-to-expected MR FLV of the contralateral lung (each p < 0.10). Patients with CDH showed a substantially lower observed-to-expected MR FLV of both lungs compared with healthy fetuses. The observed-to-expected MR FLV of both lungs as well as of the lung contralateral to the CDH were reliable prenatal predictors of survival, need for ECMO, and development of CLD.