Amy R. Mehollin-Ray

Evaluating children with fractures for child physical abuse

Fractures are common injuries caused by child abuse. Although the consequences of failing to diagnose an abusive injury in a child can be grave, incorrectly diagnosing child abuse in a child whose fractures have another etiology can be distressing for a family. The aim of this report is to review recent advances in the understanding of fracture specificity, the mechanism of fractures, and other medical diseases that predispose to fractures in infants and children. This clinical report will aid physicians in developing an evidence-based differential diagnosis and performing the appropriate evaluation when assessing a child with fractures.

Fetal lung volume and quantification of liver herniation by magnetic resonance imaging in isolated congenital diaphragmatic hernia.

To determine associations between fetal lung and liver herniation volumes measured by magnetic resonance imaging (MRI) and mortality/need for extracorporeal membrane oxygenation (ECMO) in cases of isolated congenital diaphragmatic hernia (CDH). A secondary objective was to compare prenatal MRI parameters with two‐dimensional ultrasound lung measurements.

Radiographic Abnormalities in Rothmund-Thomson Syndrome and Genotype–Phenotype Correlation with RECQL4 Mutation Status

OBJECTIVE The purpose of this study was to summarize the radiographic skeletal findings in patients with Rothmund-Thomson syndrome (RTS) and to determine whether there is an association between the presence of skeletal abnormalities and the mutational status of the RECQL4 gene. SUBJECTS AND METHODS Twenty-eight subjects with RTS underwent skeletal surveys and RECQL4 DNA mutation testing. Radiographs were reviewed by two radiologists. RECQL4 mutation testing by DNA sequencing of the gene was performed by a diagnostic laboratory. Genotype-phenotype analysis by Fishers exact test was performed to investigate whether there was a correlation between mutation status and skeletal abnormalities. RESULTS Twenty-one (75%) of the subjects had at least one significant skeletal abnormality, the more common being abnormal metaphyseal trabeculation, brachymesophalangy, thumb aplasia or hypoplasia, osteopenia, dislocation of the radial head, radial aplasia or hypoplasia, and patellar ossification defects. Three subjects had a history of destructive bone lesion (osteosarcoma). Genotype-phenotype analysis showed a significant correlation between RECQL4 mutational status and the presence of skeletal abnormalities (p < 0.0001). CONCLUSION Skeletal abnormalities are frequent in persons with RTS. Many of these abnormalities are not clinically apparent but are detectable on radiographs. The presence of skeletal abnormalities correlates with RECQL4 mutation status, which has been found to correlate with risk of osteosarcoma. Skeletal surveys aid in both diagnosis and management of RTS.

Prenatal MRI Fetal Lung Volumes and Percent Liver Herniation Predict Pulmonary Morbidity in Congenital Diaphragmatic Hernia (CDH)

PURPOSE The purpose of this study was to determine whether prenatal imaging parameters are predictive of postnatal CDH-associated pulmonary morbidity. METHODS The records of all neonates with CDH treated from 2004 to 2012 were reviewed. Patients requiring supplemental oxygen at 30 days of life (DOL) were classified as having chronic lung disease (CLD). Fetal MRI-measured observed/expected total fetal lung volume (O/E-TFLV) and percent liver herniation (%LH) were recorded. Receiver operating characteristic (ROC) curves and multivariate regression were applied to assess the prognostic value of O/E-TFLV and %LH for development of CLD. RESULTS Of 172 neonates with CDH, 108 had fetal MRIs, and survival was 76%. 82% (89/108) were alive at DOL 30, 46 (52%) of whom had CLD. Neonates with CLD had lower mean O/E-TFLV (30 vs.42%; p=0.001) and higher %LH (21.3±2.8 vs.7.1±1.8%; p<0.001) compared to neonates without CLD. Using ROC analysis, the best cutoffs in predicting CLD were an O/E-TFLV<35% (AUC=0.74; p<0.001) and %LH>20% (AUC=0.78; p<0.001). On logistic regression, O/E-TFLV<35% and a %LH>20% were highly associated with indicators of long-term pulmonary sequelae. On multivariate analysis, %LH was the strongest predictor of CLD in patients with CDH (OR: 10.96, 95%CI: 2.5-48.9, p=0.002). CONCLUSION Prenatal measurement of O/E-TFLV and %LH is predictive of CDH pulmonary morbidity and can aid in establishing parental expectations of postnatal outcomes.

Fetal MR Imaging of Congenital Diaphragmatic Hernia

Fetal magnetic resonance (MR) imaging plays a number of roles in the evaluation and management of congenital diaphragmatic hernia (CDH). Fetal MR imaging has proved valuable for anatomic assessment, determination of the specific type of CDH on the basis of which organs are involved and the effect of the hernia contents on adjacent structures, evaluation and exclusion of hernia-related complications and associated malformations (some of which may suggest an underlying syndrome), calculation of lung volume and liver herniation measurements, and calculation of the diameters of the pulmonary arteries and aorta. All of these parameters may aid the fetal care team in terms of prenatal counseling and perinatal planning. In addition, fetal MR imaging plays a role in guiding experimental fetal therapy (eg, tracheal balloon occlusion), with preliminary results showing an increase in observed-to-expected lung-to-head ratio and total fetal lung volume during the tracheal occlusion period, leading to improved neonatal survival.

Risk-stratification of severity for infants with CDH: Prenatal versus postnatal predictors of outcome

PURPOSE The purpose of this study was to compare the predication accuracy of a newly described postnatally-based clinical prediction model to fetal imaging-based predictors of mortality for infants with CDH. METHODS We performed a retrospective review of all CDH patients treated at a comprehensive fetal care center from January 2004 to January 2014. Prenatal data reviewed included lung-to-head ratio (LHR), observed/expected-total fetal lung volume (O/E-TFLV), and percent liver herniation (%LH). Based on the postnatal prediction model, neonates were categorized as low, intermediate, and high risk of death. The primary outcome was 6-month mortality. RESULTS Of 176 CDH patients, 58 had a major cardiac anomaly, and 28 had a genetic anomaly. Patients with O/E-TFLV <35% and %LH >20% were at increased risk for mortality (44% and 36%, respectively). There was a significant difference in mortality between low, intermediate, and high-risk groups (4% vs. 22% vs. 51%; p<0.001). On multivariate regression, the O/E-TFLV and postnatal-based mortality risk score were the two independent predictors of 6-month mortality. CONCLUSION The CDH Study Group postnatal predictive model provides good discrimination among three risk groups in our patient cohort. The prenatal MRI-based O/E-TFLV is the strongest prenatal predictor of 6-month mortality in infants with CDH and will help guide prenatal counseling and discussions regarding fetal intervention and perinatal management.

Fetal MRI lung volumes are predictive of perinatal outcomes in fetuses with congenital lung masses.

PURPOSE The purpose of this study was to evaluate fetal magnetic resonance imaging (MRI) as a modality for predicting perinatal outcomes and lung-related morbidity in fetuses with congenital lung masses (CLM). METHODS The records of all patients treated for CLM from 2002 to 2012 were reviewed retrospectively. Fetal MRI-derived lung mass volume ratio (LMVR), observed/expected normal fetal lung volume (O/E-NFLV), and lesion-to-lung volume ratio (LLV) were calculated. Multivariate regression and receiver operating characteristic analyses were applied to determine the predictive accuracy of prenatal imaging. RESULTS Of 128 fetuses with CLM, 93% (n=118) survived. MRI data were available for 113 fetuses. In early gestation (<26weeks), MRI measurements of LMVR and LLV correlated with risk of fetal hydrops, mortality, and/or need for fetal intervention. In later gestation (>26weeks), LMVR, LLV, and O/E-NFLV correlated with neonatal respiratory distress, intubation, NICU admission and need for neonatal surgery. On multivariate regression, LMVR was the strongest predictor for development of fetal hydrops (OR: 6.97, 1.58-30.84; p=0.01) and neonatal respiratory distress (OR: 12.38, 3.52-43.61; p≤0.001). An LMVR >2.0 predicted worse perinatal outcome with 83% sensitivity and 99% specificity (AUC=0.94; p<0.001). CONCLUSION Fetal MRI volumetric measurements of lung masses and residual normal lung are predictive of perinatal outcomes in fetuses with CLM. These data may assist in perinatal risk stratification, counseling, and resource utilization.

Fetoscopic Open Neural Tube Defect Repair: Development and Refinement of a Two-port, Carbon Dioxide Insufflation Technique

OBJECTIVE To describe development of a two-port fetoscopic technique for spina bifida repair in the exteriorized, carbon dioxide-filled uterus and report early results of two cohorts of patients: the first 15 treated with an iterative technique and the latter 13 with a standardized technique. METHODS This was a retrospective cohort study (2014-2016). All patients met Management of Myelomeningocele Study selection criteria. The intraoperative approach was iterative in the first 15 patients and was then standardized. Obstetric, maternal, fetal, and early neonatal outcomes were compared. Standard parametric and nonparametric tests were used as appropriate. RESULTS Data for 28 patients (22 endoscopic only, four hybrid, two abandoned) are reported, but only those with a complete fetoscopic repair were analyzed (iterative technique [n=10] compared with standardized technique [n=12]). Maternal demographics and gestational age (median [range]) at fetal surgery (25.4 [22.9-25.9] compared with 24.8 [24-25.6] weeks) were similar, but delivery occurred at 35.9 (26-39) weeks of gestation with the iterative technique compared with 39 (35.9-40) weeks of gestation with the standardized technique (P<.01). Duration of surgery (267 [107-434] compared with 246 [206-333] minutes), complication rates, preterm prelabor rupture of membranes rates (4/12 [33%] compared with 1/10 [10%]), and vaginal delivery rates (5/12 [42%] compared with 6/10 [60%]) were not statistically different in the iterative and standardized techniques, respectively. In 6 of 12 (50%) compared with 1 of 10 (10%), respectively (P=.07), there was leakage of cerebrospinal fluid from the repair site at birth. Management of Myelomeningocele Study criteria for hydrocephalus-death at discharge were met in 9 of 12 (75%) and 3 of 10 (30%), respectively, and 7 of 12 (58%) compared with 2 of 10 (20%) have been treated for hydrocephalus to date. These latter differences were not statistically significant. CONCLUSION Fetoscopic open neural tube defect repair does not appear to increase maternal-fetal complications as compared with repair by hysterotomy, allows for vaginal delivery, and may reduce long-term maternal risks. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, https://clinicaltrials.gov, NCT02230072.

The presence of a hernia sac in congenital diaphragmatic hernia is associated with better fetal lung growth and outcomes

PURPOSE The purpose of this study was to evaluate the relationship between the presence of a hernia sac and fetal lung growth and outcomes in infants with Congenital, Diaphragmatic Hernia (CDH). METHODS The medical records of all neonates with CDH treated in our institution between 2004 and 2011 were reviewed. The presence of a hernia sac was confirmed at the time of surgical repair or at autopsy. Data were analyzed using parametric and non-parametric tests where appropriate. Multivariable regression and survival analyses were applied. RESULTS Of 148 neonates treated for CDH, 107 (72%) had isolated CDH and 30 (20%) had a hernia sac. Infants with a hernia sac had significantly lower need for ECMO, patch repair, supplemental oxygen at 30 days of life, and shorter duration of mechanical ventilation and hospital stay. Ninety-three patients had prenatal imaging. The mean observed-to-expected total fetal lung volume in the sac group was higher throughout gestation. Although a greater percentage of sac patients had liver herniation as a dichotomous variable, the amount of herniated liver (%LH and LiTR) was significantly lower in the presence of a hernia sac. CONCLUSION The presence of a hernia sac in Congenital Diaphragmatic Hernia is associated with less visceral herniation, greater fetal lung growth, and better post-natal outcomes.

Feasibility and Outcomes of Fetoscopic Tracheal Occlusion for Severe Left Diaphragmatic Hernia.

OBJECTIVE To evaluate feasibility and initial outcomes of fetoscopic tracheal occlusion for severe diaphragmatic hernia compared with a historical cohort who had not received fetal tracheal occlusion. METHODS Outcomes in a prospective observational cohort who underwent fetoscopic tracheal occlusion for severe fetal left diaphragmatic hernia without associated anomalies were compared with our historical nontreated cohort of matched fetuses of similar severity. Fetuses were classified using the same ultrasonography and magnetic resonance imaging methodology-prospectively in the fetoscopic tracheal occlusion group and retrospectively in the historical nontreated cohort. Obstetric and postnatal outcomes were evaluated and compared. RESULTS Between January 2004 and June 2015, 218 fetuses with diaphragmatic hernia were evaluated. Twenty (9%) fetuses had severe left diaphragmatic hernia (lung-head ratio 1.0 or less and liver herniation), of which 9 of 20 were managed without tracheal occlusion. Eleven were offered the procedure and in 10, it was successful. Mean (±standard deviation) gestational age was 27.9±1.1 weeks at attempted balloon placement, 34.1±1.1 weeks at removal, and 35.3±2.2 weeks at delivery. One patient required an ex utero intrapartum treatment procedure at delivery to remove the balloon. There were no maternal complications or fetal deaths. All neonates underwent postnatal repair with a patch. The 6-month, 1-year, and 2-year survival rates were significantly higher in our treated cohort than in our nontreated historical cohort (80% compared with 11%, risk difference 69%, 95% confidence interval [CI] 38-100%, P=.01; 70% compared with 11%, risk difference 59%, 95% CI 24-94%, P=.02; and 67% compared with 11%, risk difference 56%, 95% CI 19-93%, P=.04, respectively) with reduced need for extracorporeal membrane oxygenation (30% compared with 70%, risk difference 40%, 95% CI 10-79%, P=.05). CONCLUSION Fetoscopic tracheal occlusion is feasible and is associated with improved postnatal outcomes in severe left diaphragmatic hernia. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, https://clinicaltrials.gov, NCT00881660.