The in-utero diagnosis of choledochal cyst: can postnatal imaging predict benefit from early surgical intervention?

BACKGROUND: Infants prenatally suspected of having a choledochal cyst (CDC) typically undergo ultrasound imaging shortly after birth. This study sought to evaluate features on the initial postnatal ultrasound (IPU) that could identify newborns at risk for early complications. METHODS: Following IRB approval, patients from four US fetal centers with prenatal suspicion for CDC and postnatal imaging from 2000 to 2017 were reviewed. Imaging and clinical courses were assessed. RESULTS: Forty-two patients had prenatal ultrasounds suspicious for CDC. Nineteen (45.2%) were excluded due to diagnostic revision (n = 9), cyst resolution (n = 5), lack of IPU measurements (n = 3), or lack of follow-up (n = 2). The 23 remaining patients were included in the study. Of these, five (21.7%) developed symptoms at a median age of 16.5 days (IQR 16-19 days), and 18 (78.3%) remained asymptomatic throughout the first year after birth. Five patients (21.7%) had cysts ≥ 4.5 cm on IPU (Symptomatic: n = 3; Asymptomatic: n = 2). Eighteen patients (78.3%) had cysts < 4.5 cm on IPU (Symptomatic: n = 2; Asymptomatic: n = 16). An IPU cyst size ≥ 4.5 cm was associated with neonatal symptom manifestation (p = 0.048), with 88.9% specificity (95% CI 65.3-98.6%) and 60% sensitivity (95% CI 14.7-94.7%). CONCLUSIONS: In newborns with prenatally diagnosed CDC, a cyst size ≥ 4.5 cm on IPU is associated with symptom development during the first month after birth and therefore early cyst excision is recommended.

Establishment of a multidisciplinary fetal center streamlines approach for congenital lung malformations.

PURPOSE: Fetuses with a diagnosis of congenital lung malformations (CLM) on prenatal imaging are commonly referred to a multi-disciplinary specialty team for prenatal assessment and postnatal management. The net effect of such services is broadly stated to improve the outcomes of affected newborns. However, these claims are relatively unsubstantiated. METHODS: After IRB approval, a retrospective review of children diagnosed with CLM from 2008 to 2018 and referred to a large urban children's hospital was performed. A comparison was performed between prenatally diagnosed patients having a multi-disciplinary fetal center evaluation (FC) and prenatally diagnosed patients who did not receive a referral or were seen prior to the establishment of the center (NON-FC). RESULTS: Eighty-eight live-born patients with a prenatal diagnosis of CLM were identified, with 49 in the FC group and 39 NON-FC. Thirty-four (63%) and 23 (59%) patients underwent operative resection of CLM, respectively. FC patients presented earlier at first postnatal follow-up (42 vs. 145 days, p = .03), had fewer preoperative office visits (2.1 vs. 3.4, p = .0003), received fewer preoperative chest radiographs (0.5 vs. 1.3; p = .002) and chest computed tomography (0.9 vs. 1.4; p = .001), and had fewer preoperative pneumonias (0 vs. 17.4%; p = .02) compared to their NON-FC counterparts. FC patients were also more likely to undergo resection at an earlier age (217 vs. 481 days, p = .003) and were more likely to undergo a minimally invasive resection (75% vs. 39.1%, p = .015). There were no differences in post-operative outcomes between the two groups. CONCLUSION: Children with a prenatal diagnosis of CLM appear to benefit from an organized multi-specialty team approach in several impactful parameters. Hospital systems and providers that invest in similar strategies are likely to achieve improved outcomes in the care of newborns prenatally diagnosed with a CLM.

Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Twin-twin transfusion syndrome complicated by single ventricle physiology: A case report.

Clinically significant extrauterine twin-twin transfusion syndrome in conjoined twins is rare and carries a high risk of perinatal mortality. The ensuing postnatal imbalance in circulation across connecting vessels results in hypovolemia in the donor and hypervolemia in the recipient. Data on management and treatment are sparse especially in the setting of a single ventricle congenital heart defect. We present a case of a pair of omphalopagus conjoined twins, one with a single ventricle physiology (Twin B), who developed twin-twin transfusion syndrome shortly after birth. The resulting pathophysiology in the setting of a single ventricle congenital heart defect created added layers of complexity to their management and expedited surgical separation. Shunting from Twin B to Twin A-with an anatomically normal heart-resulted in mal-perfusion and rapid deterioration jeopardizing the health of both twins. In the preoperative course, steps taken to medically optimize the twins prior to surgery and the anesthetic considerations are detailed in this report.

Impact of Additional Anomalies on Postnatal Outcomes in Congenital Lung Malformations.

BACKGROUND: Approximately 20% of fetuses diagnosed with congenital lung malformations (CLMs) are found to have additional anomalies. We aim to determine if additional anomalies have an impact on postnatal outcomes for patients with CLMs. METHODS: After institutional review board approval, we performed a retrospective review of live-born patients with CLMs from 2008 to 2018. All patients were prenatally diagnosed with CLMs. Clinical information pertaining to additional congenital anomalies and outcomes was collected from the electronic health record and analyzed. RESULTS: Of the 88 patients who had a prenatal diagnosis of CLMs, 20.5% had additional anomalies. Ten of the 18 patients (56%) were considered to have a major anomaly in addition to CLMs. Outcomes for patients electing nonoperative management of CLMs were similar between those with and without an additional anomaly. Although patients with an additional anomaly were more likely to have perinatal respiratory complications (44% versus 17%, P = 0.03), the number of preoperative clinic and emergency department visits, age at surgery, minimally invasive approach to surgical resection of CLM, estimated blood loss, length of hospital stay, intubation, duration of intubation, 30-day postoperative complications, and long term sequelae were not statistically different. This held true when stratified for major versus minor anomalies. CONCLUSIONS: Twenty percent of fetuses diagnosed with CLM in our population have additional anomalies. Newborns with additional anomalies have a higher risk of pre-excision pulmonary complications. However, the overall outcomes of all patients with CLMs are similar.

Comparative outcomes of right versus left congenital diaphragmatic hernia: A multicenter analysis.

BACKGROUND: Congenital diaphragmatic hernia (CDH) occurs in 1 out of 2500-3000 live births. Right-sided CDHs (R-CDHs) comprise 25% of all CDH cases, and data are conflicting on outcomes of these patients. The aim of our study was to compare outcomes in patients with right versus left CDH (L-CDH). METHODS: We analyzed a multicenter prospectively enrolled database to compare baseline characteristics and outcomes of neonates enrolled from January 2005 to January 2019 with R-CDH vs. L-CDH. RESULTS: A total of 588, 495 L-CDH, and 93 R-CDH patients with CDH were analyzed. L-CDHs were more frequently diagnosed prenatally (p=0.011). Lung-to-head ratio was similar in both cohorts. R-CDHs had a lower frequency of primary repair (p=0.022) and a higher frequency of need for oxygen at discharge (p=0.013). However, in a multivariate analysis, need for oxygen at discharge was no longer significantly different. There were no differences in long-term neurodevelopmental outcomes assessed at two year follow up. There was no difference in mortality, need for ECMO, pulmonary hypertension, or hernia recurrence. CONCLUSION: In this large series comparing R to L-CDH patients, we found no significant difference in mortality, use of ECMO, or pulmonary complications. Our study supports prior studies that R-CDHs are relatively larger and more often require a patch or muscle flap for repair. TYPE OF STUDY: Prognosis study LEVEL OF EVIDENCE: Level II.

Role of Nerve and Muscle Biopsies in Pediatric Patients in the Era of Genetic Testing.

BACKGROUND: An operative biopsy is an important component in the diagnosis and treatment of neuromuscular disorders (NMDs). However, recent advances in molecular genetics suggest less invasive genetic testing should be the initial approach. The purpose of our study was to demonstrate the diagnostic value of muscle or nerve biopsy within the pediatric population at a pediatric academic center and offer recommendations for genetic testing in relation to biopsy to achieve the highest diagnostic yield. METHODS: Following institutional review board approval, we retrospectively reviewed the electronic medical record of 221 pediatric patients who underwent muscle and/or nerve biopsy for suspicion of NMD from January 2007 to March 2018. Demographics, family history, clinical presentations, genetic testing results, pathology results, anesthesia complications, clinical diagnoses, and clinic follow-up data were collected. Chi-square analysis was done for statistical significance. RESULTS: A total of 220 underwent muscle biopsy, and 15 underwent nerve biopsy. Not all patients received genetic testing. The average age at biopsy was 7.7 y. Biopsy revealed significant histologic abnormalities in 62.9% (139), directly leading to a specific clinical diagnosis in 33.9% (75). When genetic testing was done before biopsy, definite pathogenic variants were found in 7.6% (9). When genetic testing was done after biopsy, definite pathogenic variants were found in 45.0% (27). Genetic testing yield for pathogenic variants was higher when done after biopsy (P value < 0.00001). CONCLUSIONS: Muscle and nerve biopsies may provide significant diagnostic value. Biopsy helped to rule in or out NMD and guide genetic testing. Our data suggest NMD genetic testing yield was higher when done after biopsy.

Does Age Affect Surgical Outcomes After Ileal Pouch-Anal Anastomosis in Children?

BACKGROUND: Younger children are referred for surgical intervention in the treatment of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Outcome data in this population after a laparoscopic restorative proctocolectomy and Ileal pouch-anal anastomosis (LRS-IPAA) are limited. We reviewed our experience to determine if younger children would have similar functional outcomes. METHODS: After institutional review board approval, a review of children with FAP and UC undergoing LRS-IPAA at a children's hospital from 2002 to 2017 occurred. The study groups were defined based on age: young group (YG; 5-12 y) and older group (OG; 13-18 y). Data points included demographics, postprocedure course, and outcomes. Statistical analysis was performed. RESULTS: Sixty-five children were identified and grouped by age: YG (n = 22, average age 9 y) and OG (n = 43, average age 15.4 y). Thirteen children in YG had UC, and nine had FAP. Twenty-eight children in OG were diagnosed with UC, and 15 with FAP. After LRS-IPAA, continence, appetite recovery, and use of antidiarrheal medications were not significantly different between groups. The incidence of pouch stricture, diagnosis of pouchitis, and complications were also not significantly different. Two children (YG), aged 11 and 12 y at the time of colectomy, were initially diagnosed with UC and then reassigned as having Crohn's disease because of persistent symptoms. One child, who underwent colectomy at 17 y for FAP, had invasive rectal cancer and died 3 y later from metastatic disease. Time of follow-up for OG is 8-61 mo (average: 37 mo). Period of follow-up for YG is 11-73 mo (average: 43 mo). CONCLUSIONS: There are no significant differences in the functional outcomes between groups after LRS-IPAA. Although numbers are small, these data suggest younger age should not be a deterrent when contemplating LRS-IPAA in the treatment of UC and FAP in the pediatric population. Younger patients with FAP may benefit from early intervention.

Outcomes following two-stage surgical approaches in the treatment of pediatric ulcerative colitis.

INTRODUCTION: Surgery for the treatment of ulcerative colitis (UC) can be performed in one-, two-, or three-stage procedures [1]. The more traditional approach is a total proctocolectomy and creation of an ileo pouch-anal anastomosis and diverting stoma at the initial operation, followed by ileostomy closure several weeks later (TIPPA) [1]. An alternative is an initial subtotal colectomy and end ileostomy [2]. In this alternative approach (NIPAA), a completion proctectomy and definitive ileo pouch-anal anastomosis can be performed without a diverting stoma. We hypothesize that functional outcomes following a NIPAA approach when performed in children, in our experience, are likely similar or improved when compared to those treated by TIPAA. METHODS: After IRB approval, a review of patients who underwent a two-stage Laparoscopic IPAA from 2004 to 2017 occurred. Data included demographics, diagnosis, surgical intervention time to full diet, level of continence, use of antidiarrheals and complications. RESULTS: N = 41 (NIPAA = 14, TIPAA = 27). After establishment of bowel continuity, no significant differences in appetite recovery, continence, or complications were noted. The number of antidiarrheals prescribed were significantly higher in the TIPAA group (p = 0.01). Thirteen patients (31.7%) had pouchitis: 4 NIPAA and 9 TIPAA (p = NS). Of the 41 patients, 11 required subsequent surgery; 2 patients (18.2%) received NIPAA and 9 (81.8%) received TIPAA (p = 0.20). Two TIPAA patients received a diverting ileostomy owing to chronic anal pain and failure to achieve continence. CONCLUSION: This study suggests children with medically refractory UC treated by NIPAA or TIPAA have similar outcomes. Minimal differences in overall outcome were noted following either approach. However, NIPAA may reduce reliance on antidiarrheals to achieve satisfactory defecation outcomes. LEVEL OF EVIDENCE: III Retrospective comparative study.

Fetal Head and Neck Masses: MRI Prediction of Significant Morbidity.

OBJECTIVE: The purpose of this study is to determine which MRI parameters of fetal head and neck masses predict high-morbidity neonatal outcomes, including ex utero intrapartum treatment (EXIT) procedure. MATERIALS AND METHODS: This retrospective study (2004-2016) included parameters of polyhydramnios (based on largest vertical pocket), mass effect on the trachea, mass midline extension, and morphologic grade and size of masses. The morbid cohort included those requiring an EXIT procedure, difficult intubation at delivery, or lethal outcome. Predictive modeling with a multivariable logistic regression and ROC analysis was then performed. RESULTS: Of 36 fetuses, five were delivered by EXIT procedures, there was one neonatal death within 12 hours after delivery, and another neonate required multiple intubation attempts. The remaining 29 fetuses were delivered at outside institutions with no interventions or neonatal morbidity. The largest vertical pocket and mass effect on the trachea were selected as independent predictors by the logistic regression. The cross-validated ROC AUC was 0.951 (95% CI, 0.8795-1). CONCLUSION: The largest vertical pocket measurement and mass effect on the trachea were the most contributory MRI parameters that predicted significant morbidity in fetuses with masses of the face and neck, along with other significant parameters. These parameters predict significant morbid neonatal outcomes, including the need for EXIT procedures.