Emily A. Partridge

Preschool neurological assessment in congenital diaphragmatic hernia survivors: Outcome and perinatal factors associated with neurodevelopmental impairment

OBJECTIVE To evaluate the preschool neurodevelopmental outcome in CDH survivors between 2 and 5 years of age and to identify perinatal and postnatal factors that may be predictive of persistent neurological deficits. METHODS The study cohort consists of 60 CDH survivors that were enrolled in our prospective, follow-up program between January 2006 and September 2012. Developmental assessment of study participants between 2 and 3 years of age was performed using the Bayley Scales of Infant Development, 3rd Edition (BSID-III). Cognitive outcomes of CDH children older than 3 years of age were evaluated using The Wechsler Preschool and Primary Scale of Intelligence, 3rd Edition (WPPSI-III). Neurodevelopmental delay was defined by a score of ≤ 85 in any of the evaluated composite scores. Severe impairments were defined as a score of ≤ 69 in at least one domain tested. RESULTS Mean follow-up for children assessed by BSID-III (n=42) and WPPSI-III (n=18) was 28 ± 4.5 months and 58 ± 4.0 months, respectively. As a group, mean composite and subdomain BSID-III and WPPSI-III scores were within the expected normal range. For the BSID-III group, 9 (22%) had mild deficits in at least one domain, and 6 (14%) had severe deficits in at least one. Only 3 (7%) patients demonstrated severe neurological delays for all BSID-III composite scales. For the WPPSI-III group, 4 (22%) patients scored within the borderline-delayed range for at least one subscale and only one (6%) child had a WPPSI-III VIQ score in the severe delay range. Abnormal muscle tonicity was found in 35% (hypotonicity 33%, hypertonicity 2%). Need for ECMO, prolonged ventilation, hypotonicity, and other surrogate markers of disease severity (P<0.05) were associated with borderline or delayed neurological outcome. CONCLUSION The majority of CDH children are functioning in the average range at early preschool and preschool age. Neuromuscular hypotonicity is common in CDH survivors. CDH severity appears to be predictive of adverse neurodevelopmental outcome.

Timing of repair of congenital diaphragmatic hernia in patients supported by extracorporeal membrane oxygenation (ECMO)

PURPOSE The optimal timing of repair for congenital diaphragmatic hernia (CDH) in patients requiring extracorporeal membrane oxygenation (ECMO) is controversial. Repair during ECMO may improve respiratory function by restoring normal anatomy. However, there is increased risk of complications including surgical bleeding. The purpose of this study was to examine the impact of timing of CDH repair on outcomes in a large cohort of patients treated at a single institution. METHODS We retrospectively reviewed charts of all CDH patients in our Pulmonary Hypoplasia Program from 2004 to 2013. Categorical variables were analyzed by Fishers exact test and continuous variables by Mann-Whitney t-test (p<0.05). RESULTS A total of 77 CDH patients required ECMO support during the study dates. Of these, 16 patients did not survive to repair, 3 patients were repaired prior to cannulation, 41 patients were repaired during ECMO, and 17 patients were repaired after decannulation. Survival was 67%, 43.9%, and 100% for those repaired prior to, during, or post ECMO, respectively, with statistical significance associated with repair after decannulation (P<0.0001). Operative bleeding requiring transfusion occurred in 12 patients repaired on ECMO, while no significant bleeding occurred in patients repaired after decannulation (P=0.003). CONCLUSION Outcomes were improved in CDH patients undergoing surgical repair following ECMO with significantly increased survival, lower rates of surgical bleeding, and decreased total duration of ECMO therapy compared to patients repaired on ECMO. In patients who can be successfully weaned from ECMO, our study supports a role for delayed repair off ECMO with reduced operative morbidity and increased survival.

Incidence and factors associated with sensorineural and conductive hearing loss among survivors of congenital diaphragmatic hernia

PURPOSE The reported incidence of sensorineural hearing loss (SNHL) in long-term survivors of congenital diaphragmatic hernia varies widely in the literature. Conductive hearing loss (CHL) is also known to occur in CDH patients, but has been less widely studied. We sought to characterize the incidence and risk factors associated with SNHL and CHL in a large cohort of CDH patients who underwent standardized treatment and follow-up at a single institution. METHODS We retrospectively reviewed charts of all CDH patients in our pulmonary hypoplasia program from January 2004 through December 2012. Categorical variables were analyzed by Fishers exact test and continuous variables by Mann-Whitney t-test (p≤0.05). RESULTS A total of 112 patients met study inclusion criteria, with 3 (2.7%) patients diagnosed with SNHL and 38 (34.0%) diagnosed with CHL. SNHL was significantly associated with requirement for ECMO (p=0.0130), prolonged course of hospitalization (p=0.0011), duration of mechanical ventilation (p=0.0046), requirement for tracheostomy (p=0.0013), and duration of loop diuretic (p=0.0005) and aminoglycoside therapy (p=0.0003). CONCLUSIONS We have identified hearing anomalies in over 30% of long-term CDH survivors. These findings illustrate the need for routine serial audiologic evaluations throughout childhood for all survivors of CDH and stress the importance of targeted interventions to optimize long-term developmental outcomes pertaining to speech and language.

Urologic and anorectal complications of sacrococcygeal teratomas: Prenatal and postnatal predictors

PURPOSE Anorectal and urologic sequelae are observed in long-term survivors of sacrococcygeal teratoma (SCT). In this study we evaluate the incidence and predictors of anorectal and urologic complications in SCT. METHODS A retrospective review was performed for all SCT patients who underwent resection at a single institution between 2000 and 2012. Enrollment criteria included a minimum of 12months follow-up. Categorical variables were analyzed by Fishers exact test and continuous variables by Mann Whitney test (p<0.05). RESULTS Forty-five patients were studied. Anorectal complications occurred in 29%, including severe chronic constipation (n=13) and fecal incontinence (n=4). Urologic complications occurred in 33%, including neurogenic bladder (n=12), vesicoureteral reflux (n=5), and urinary incontinence (n=7). Prenatal imaging by fetal MRI demonstrated mass effect with obstruction of the bowel (n=4) or bladder and collecting system (n=7) in a subset of patients with postnatal complications (anorectal 4/4, PPV 100%; urologic 6/7, PPV 86%). Postnatal complications were associated with obstructive findings on prenatal imaging, prenatal therapeutic interventions, Altman classification, perineal reconstruction, and tumor recurrence. No anorectal or urologic complications occurred in patients with Altman type I tumors. CONCLUSIONS Urologic and anorectal complications are common in patients with SCT. Higher Altman classification and prenatal imaging suggestive of intestinal or urologic obstruction should prompt focused prenatal counseling and postnatal screening for anorectal and urologic dysfunction.

Right- versus left-sided congenital diaphragmatic hernia: a comparative outcomes analysis

PURPOSE Right-sided congenital diaphragmatic hernia (R-CDH) occurs in up to 25% of all CDH cases, but has been less widely studied compared to left-sided defects. We sought to compare characteristics and outcomes of left- versus right-sided defects in a large cohort of CDH patients who underwent standardized treatment and follow-up at a single institution. METHODS We retrospectively reviewed charts of all CDH patients in our pulmonary hypoplasia program from January 2002 through December 2014. Categorical variables were analyzed by Fishers exact test and continuous variables by Mann-Whitney t-test (p≤0.05). RESULTS A total of 330 CDH patients were treated more than the 12-year study period, with 274 (83%) left-sided and 56 (17%) right-sided cases identified. Specific pulmonary morbidities were associated with R-CDH, with increased duration of nitric oxide therapy, increased requirement for tracheostomy, increased requirement for supplemental oxygen at the time of NICU discharge, and increased chronic pulmonary hypertension with requirement for long-term Sildenafil therapy. CONCLUSIONS In this series, R-CDH was not associated with increased mortality, but was associated with increased requirement for pulmonary vasodilatory therapy and requirement for tracheostomy. The high incidence of pulmonary complications indicates increased severity of pulmonary hypoplasia in R-CDH, supporting a role for delivery in tertiary centers with expertise in CDH management.

Pulmonary hypertension in giant omphalocele infants

BACKGROUND Pulmonary hypoplasia has been described in cases of giant omphalocele (GO), although pulmonary hypertension (PH) has not been extensively studied in this disorder. In the present study, we describe rates and severity of PH in GO survivors who underwent standardized prenatal and postnatal care at our institution. METHODS A retrospective chart review was performed for all patients in our pulmonary hypoplasia program with a diagnosis of GO. Statistical significance was calculated using Fishers exact test and Mann-Whitney test (p<0.05). RESULTS Fifty-four patients with GO were studied, with PH diagnosed in twenty (37%). No significant differences in gender, gestational ages, birth weight, or Apgar scores were associated with PH. Patients diagnosed with PH were managed with interventions, including high frequency oscillatory ventilation, and nitric oxide. Nine patients required long-term pulmonary vasodilator therapy. PH was associated with increased length of hospital stay (p<0.001), duration of mechanical ventilation (p=0.008), and requirement for tracheostomy (p=0.0032). Overall survival was high (94%), with significantly increased mortality in GO patients with PH (p=0.0460). Prenatal imaging demonstrating herniation of the stomach into the defect was significantly associated with PH (p=0.0322), with a positive predictive value of 52%. CONCLUSIONS In this series, PH was observed in 37% of GO patients. PH represents a significant complication of GO, and management of pulmonary dysfunction is a critical consideration in improving clinical outcomes in these patients.

Brain-type natriuretic peptide levels correlate with pulmonary hypertension and requirement for extracorporeal membrane oxygenation in congenital diaphragmatic hernia

PURPOSE B-type natriuretic peptide (BNP), an established biomarker of ventricular pressure overload, is used in the assessment of children with pulmonary hypertension (PH). PH is commonly observed in congenital diaphragmatic hernia (CDH). However, the use of BNP levels to guide treatment in this patient population has not been well defined. In this study, we investigate BNP levels in a large cohort of CDH patients treated at a single institution. METHODS We retrospectively reviewed charts of all CDH patients enrolled in our pulmonary hypoplasia program from 2004-2013. PH was assessed by echocardiography using defined criteria, and patients were further stratified into the following cohorts: no PH, short-term PH (requiring nitric oxide but no additional vasodilatory therapy), long-term PH (requiring continued vasodilatory therapy post-discharge), and ECMO (requiring ECMO therapy). RESULTS A total of 132 patients were studied. BNP levels were significantly increased in patients with PH compared to patients with normal pulmonary pressures (P<0.01). BNP levels were not significantly different between the ST-PH, LT-PH, and ECMO cohorts, but all levels in all three cohorts were significantly increased compared to patients who did not develop PH. CONCLUSION Our findings indicate that plasma BNP levels correlate with pulmonary hypertension as well as the requirement for ECMO in CDH patients. Monitoring of serial BNP levels may provide a useful prognostic tool in the management of CDH.

Systemic hypertension in giant omphalocele: An underappreciated association

PURPOSE To evaluate the incidence, severity and duration of systemic hypertension in infants born with giant omphalocele (GO). METHODS A retrospective review of patients born from 2003 through 2013 with a GO or intestinal atresia (control population) and managed at a single institution was performed. The hospital course was reviewed including all blood pressures, method of omphalocele repair, requirement for antihypertensive medications and renal function. RESULTS Forty-five GO and 20 control patients met criteria for the study. Thirty-three GO patients underwent Schuster repair and 12 GO patients underwent delayed repair after epithelialization. Overall, 78% of GO patients had episodes of hypertension (82% Schuster and 67% delayed repair) compared to 15% of control patients (P<0.001). The majority of episodes were transient and occurred in the postoperative period (97%). Hypertension was persistent in 4 GO patients. These patients required antihypertensive medication at discharge, which was discontinued as an outpatient. No patient demonstrated significant evidence of renal abnormalities as indicated by renal ultrasound, urinalysis and/or serum creatinine level at the time of hypertension. CONCLUSION Episodes of systemic hypertension are frequent in patients with GO. Episodes are often post-operative, transient and can be present in patients undergoing either a delayed or Schuster repair. A small subset of patients will have persistent hypertension requiring antihypertensive medication that can be weaned off in an outpatient setting.

Maternal–fetal surgery for structural malformations

Although most prenatally diagnosed correctable anatomic abnormalities are best addressed by surgical interventions after birth, the outcomes of a small number of severe structural malformations with predicted fetal demise or devastating sequelae postnatally may be improved by correction before birth. Consideration of maternal-fetal surgical intervention is restricted to those anatomic malformations that interfere with normal organ development and which, if alleviated, may permit normal development to proceed. Advances in prenatal diagnosis and technical innovations in the surgical approach to the fetus have resulted in an increase in the successful clinical application of fetal intervention over the past 3 decades. The purpose of this review is to describe the current status of maternal-fetal surgery, with a focus on the congenital anomalies most commonly treated by intervention before birth, and to highlight the key areas for further research in this evolving surgical specialty.

Prenatal diagnosis of esophageal bronchus — first report of a rare foregut malformation in utero

AIM OF THE STUDY Esophageal bronchus is a rare bronchopulmonary foregut malformation in which an isolated portion of the respiratory system communicates with the esophagus. There are no reports of prenatal diagnosis of an esophageal bronchus in the literature. We present 5 cases of esophageal bronchus and describe unique imaging findings. METHODS Following IRB approval, 5 cases of pathologically proven esophageal bronchus were identified from a single center fetal therapy surgical database. Prenatal magnetic resonance and ultrasound studies were scored for the presence of bronchoceles, cysts, vascular feeders, and location. Five control cases were selected from a radiology database, with lesions determined to represent bronchial atresia prenatally and located at the lung bases. All imaging was reviewed blinded to outcome. MAIN RESULTS A tubular T2 hyperintense structure (bronchocele) directed from the lung lesion to the gastroesophageal junction was seen in all cases of esophageal bronchus, but in none of the control cases. In all control cases, the bronchocele was directed to the pulmonary hilum. The presence of cysts or vascular feeding vessels was not statistically significant in identifying an esophageal bronchus lesion. All patients were delivered at term and underwent surgical resection between 5 to 19 weeks of age. No postoperative complications occurred. CONCLUSION Prenatal diagnosis of an esophageal bronchus can be strongly suggested by the presence of a T2 hyperintense structure arising from a lung lesion and directed towards the GE junction. These findings may be helpful for better counseling of parents and improved surgical planning.