Adesola C. Akinkuotu

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.

Predictors of poor prognosis in prenatally diagnosed sacrococcygeal teratoma: A multiinstitutional review

INTRODUCTION Attempts at defining predictors of poor outcome in fetal sacrococcygeal teratoma (SCT) have been hampered by small patient numbers. We sought to validate the utility of tumor volume to fetal weight ratio (TFR) as a predictor of poor prognosis and to identify other morphological outcome predictors in a multicenter series. METHODS Records of prenatally diagnosed SCT at three fetal centers from 1986 to 2011 were reviewed. Prenatal imaging characteristics including TFR, morphology, hydrops, and placentomegaly were assessed. Poor prognosis was defined as fetal demise, need for fetal intervention, or perinatal death. Receiver operating characteristic (ROC) analysis was used to select a TFR cutoff value. RESULTS Seventy-nine fetuses with SCT were evaluated. Eleven pregnancies ending in elective termination were excluded. ROC analysis revealed that TFR >0.12 prior to 24 weeks gestation was predictive of poor prognosis (AUC=0.913; Sensitivity=91.7%, Specificity=76.2%, PPV=86.8%; NPV=84.2%). Solid tumor morphology and presence of hydrops were found to be predictors of poor prognosis. None of the factors associated with poor prognosis were independent predictors on multivariate analysis. CONCLUSION This study validates TFR >0.12 prior to 24 weeks gestation as an objective predictor of outcomes in fetuses with SCT that can be easily applied in most clinical settings.

Prenatally diagnosed neck masses: long-term outcomes and quality of life.

PURPOSE To determine long-term outcomes of fetuses with neck masses (NM), including functional and cosmetic results. METHODS A retrospective review was performed of all fetuses evaluated for NM from November 2001 to March 2014. Quality of life (QOL) was evaluated using the validated PedsQL™ questionnaire. RESULTS Of 35 fetuses evaluated, 9 died perinatally and 1 died late from tracheostomy complications. NM ranged from 4 to 20cm (mean, 9.1cm); 18 were delivered by EXIT. Of 25 surviving patients, 22 had mass resection, 7 requiring more than one procedure. Surviving patients with lymphatic malformations (LM) had the highest incidence of moderate and severe disfigurement and a higher rate of persistent/recurrent disease (100% vs. 31%, p=0.002) and cranial nerve dysfunction (50% vs. 0%, p=0.005) compared to those with non-LM diagnoses. Of 9 children attending school, 78% achieve grades of A/Bs. QOL for 13 patients revealed a mean score of 83/100 for physical and 78/100 for psychosocial functioning. Median follow-up was 6 years (7 months-17 years). CONCLUSION Unlike those with teratoma or other lesions, children with congenital cervicofacial LM are at high-risk for persistent disease, nerve dysfunction and moderate-severe disfigurement. There is substantial perinatal morbidity for fetuses with neck masses, but for those surviving, the long-term functional and cognitive outcomes are good.

Are all pulmonary hypoplasias the same? A comparison of pulmonary outcomes in neonates with congenital diaphragmatic hernia, omphalocele and congenital lung malformation

INTRODUCTION Patients with congenital diaphragmatic hernias (CDH), omphaloceles, and congenital lung malformations (CLM) may have pulmonary hypoplasia and experience respiratory insufficiency. We hypothesize that given equivalent lung volumes, the degree of respiratory insufficiency will be comparable regardless of the etiology. METHODS Records of all fetuses with CDH, omphalocele, and CLM between January 2000 and June 2013 were reviewed. MRI-based observed-to-expected total fetal lung volumes (O/E-TFLV) were calculated. An analysis of outcomes in patients with O/E-TFLV between 40% and 60%, the most inclusive range, was performed. RESULTS 285 patients were evaluated (161, CDH; 24, omphalocele; 100, CLM). Fetuses with CDH had the smallest mean O/E-TFLV. CDH patients were intubated for longer and had a higher incidence of pulmonary hypertension. Fifty-six patients with the three diagnoses had an O/E-TFLV of 40%-60%. The need for ECMO, supplemental oxygen at 30days of life, and 6-month mortality were similar among groups. CDH patients had a significantly longer duration of intubation and higher incidence of pulmonary hypertension than the other two diagnoses. CONCLUSION Given equivalent lung volumes (40%-60% of expected), CDH patients require more pulmonary support initially than omphalocele and CLM patients. In addition to lung volumes, disease-specific factors, such as pulmonary hypertension in CDH, also contribute to pulmonary morbidity and overall outcome.

An evaluation of the role of concomitant anomalies on the outcomes of fetuses with congenital diaphragmatic hernia.

PURPOSE The purpose of this study was to evaluate the impact of various types of associated anomalies on CDH mortality and morbidity. METHODS All CDH patients at a tertiary care center from January 2004 to January 2014 were reviewed retrospectively. Isolated CDH was defined as CDH without any associated anomalies. Cardiac anomalies were stratified into minor and major based on the Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) scoring system. Other anatomic anomalies requiring intervention in the perinatal period were classified as major anomalies. The outcomes of interest were 6-month mortality as well as pulmonary and gastrointestinal morbidity. RESULTS Of 189 CDH patients, 93 (49%) had isolated CDH. Others had: cardiac anomalies alone (n=47, 25%), genetic anomalies (n=28, 15%), structural anomalies alone (n=18, 10%), and both cardiac and genetic anomalies (n=20, 11%). Fifty (26.5%) patients were dead before six months of age. Mortality rate at 6months was higher in patients with genetic and major cardiac anomalies. A major cardiac anomaly was independently associated with a 102-fold increased risk of mortality at 6months (95%CI: 3.1-3402). Pulmonary morbidity was increased in patients with genetic, major cardiac, and major structural anomalies, while gastrointestinal morbidity was higher in patients with major structural anomalies alone. CONCLUSION Major cardiac and genetic anomalies were associated with increased 6-month mortality in CDH patients. However, the association with minor cardiac anomalies and/or structural anomalies did not affect mortality and morbidity of CDH patients. The presence of minor anomalies should not adversely impact their perinatal management or consideration for in-utero therapy.

Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain

BACKGROUND Advances in surgery and technology have resulted in increased in-utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. OBJECTIVE The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. STUDY DESIGN Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% × 1 hour, 4% × 3 hours, or 2% × 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. RESULTS A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2% isoflurane exposure compared to controls (1.57 ± 0.22 × 10(6)/mm(3) vs 1.01 ± 0.44 × 10(6)/mm(3), P = .02). Fetuses at 70 days gestation with repeated exposure demonstrated decreased frontal cortex neurons at day 130 when compared to age-matched controls (2.42 ± 0.3 × 10(5)/mm(3) vs 7.32 ± 0.4 × 10(5)/mm(3), P = .02). No significant difference in neuroapoptosis was observed between the repeated exposure group and controls in the hippocampus, cerebellum, or basal ganglia. CONCLUSION Repeated isoflurane exposure in midgestation sheep resulted in increased frontal cortex neuroapoptosis. This persisted into late gestation as decreased neuronal cell density. While animal studies should be extrapolated to human beings with caution, our findings suggest that the number of anesthetic/sedative exposures should be considered when contemplating the risks and benefits of fetal intervention as certain fetal therapies may need to be repeated.

Assessment of quality of life outcomes using the pediatric quality of life inventory survey in prenatally diagnosed congenital diaphragmatic hernia patients.

INTRODUCTION Congenital diaphragmatic hernia patients can have significant postnatal morbidity. To date, there has been no quality of life (QOL) study in a prenatally diagnosed CDH patient population, assessing prenatal disease severity and QOL. The purpose of this pilot study was to assess the QOL in a single institution fetal center CDH experience. METHODS The study was a retrospective cohort study of CDH patients diagnosed by fetal ultrasound and MRI at a fetal center between March 2002-March 2014. Parents of children ≥2years were contacted by telephone to participate in the validated Pediatric Quality of Life Inventory (PedsQL™, Version 4.0). RESULTS Of 95 CDH survivors, 68 met inclusion criteria, of which 28 (42%) completed the survey (mean age, range: 5.5, 2.3-11.7years). Based on prenatal markers of disease severity, there were no differences in performance between those with mild or severe forms of CDH. Overall, patients had minimal QOL limitations, but those with limitations had a higher risk for oxygen dependence at 30days of life (71%v. 29%, OR 0.16, CI, 0.031-0.82, p=0.02). ECMO was not associated with significantly worse QOL in physical or psychosocial functioning. Cronbachs alpha reliability coefficient yielded a correlation of 0.951 for the overall survey, 0.911 for physical functioning, and 0.901 for psychosocial functioning questions. CONCLUSIONS Patients that are prenatally diagnosed with severe forms of CDH have similar QOL outcomes across all categories of physical and psychosocial functioning. This pilot study is encouraging and may allow improved counseling for expectant parents of CDH patients.

The use of an institutional pediatric abdominal trauma protocol improves resource use.

BACKGROUND A novel protocol to standardize the emergency center (EC) management of abdominal trauma in children was developed and implemented at our trauma center. The purpose of this study was to evaluate whether this protocol improved patient safety by decreasing unnecessary computed tomography (CT) radiation and improved quality of care by decreasing EC length of stay (LOS) and laboratory costs. METHODS We performed a prospective, longitudinal study of children who presented to the EC with a mechanism for abdominal trauma and received an abdominal CT scan from January 2011 to September 2014. Patients were divided into protocol periods: preimplementation (January 2011 to December 2011), Postimplementation 1 (January 2012 to August 2013), and Postimplementation 2 (September 2013 to September 2014). Outcome measures included protocol adherence, rates of clinically positive CT results, the EC LOS, and the cost of laboratory studies. &khgr;2 and analysis of variance were used for statistical analysis. RESULTS During the study period, 117 patients in the preimplementation, 148 patients in the Postimplementation 1, and 56 patients in the Postimplementation 2 periods were identified. Protocol adherence improved from 70% to 82% (p = 0.11) from the Postimplementation 1 to Postimplementation 2 periods. The rate of positive CT scan results increased from 23% to 31% to 46% (p = 0.003) from preimplementation to Postimplementation 1 and Postimplementation 2, respectively. When the protocol was followed, the proportion of clinically significant scans was higher than when it was not followed (31% vs. 8%, p = 0.001). The EC LOS was unchanged (median [range], 271 minutes [16–1,039 minutes] vs. 233 minutes [40–1,396 minutes], p = 0.34). The median cost of laboratory studies remained the same from preimplementation to Postimplementation 1 (

A novel multimodal computational system using near-infrared spectroscopy to monitor cerebral oxygenation during assisted ventilation in CDH patients.

166 [

Persistent hypercarbia after resuscitation is associated with increased mortality in congenital diaphragmatic hernia patients

0–