Effect of single and multiple courses of maternal betamethasone on prenatal congenital lung lesion growth and fetal survival.

PURPOSE: Administration of maternal betamethasone (BMZ) is a therapeutic option for fetuses with large microcystic congenital lung lesions at risk for, or causing, hydrops. Not all fetuses respond to a single course of BMZ. We review our experience with the use of single and multiple courses of maternal BMZ for the management of these patients. METHODS: A retrospective review of fetuses with congenital lung lesions managed with maternal BMZ from 2003 to 2014 was performed. RESULTS: Forty-three patients were managed with prenatal steroids (28 single course, 15 multiple courses). Single course recipients demonstrated a reduction in lesion size and resolution of hydrops in 82% and 88% of patients respectively compared to 47% and 56% in recipients of multiple steroid courses. Survival of multiple course patients (86%) was comparable to that of single course patients (93%) and improved compared to non-treated historical controls. Multiple course recipients demonstrated an increased need for open fetal surgery and postnatal surgery at a younger age. CONCLUSION: Fetuses who fail to respond to a single course of BMZ may benefit, as indicated by hydrops resolution and improved survival, from additional courses. However, failure to respond is indicative of a lesion which may require fetal or immediate neonatal resection.

Chorioamniotic membrane separation and preterm premature rupture of membranes complicating in utero myelomeningocele repair.

BACKGROUND: Since the results of the Management of Myelomeningocele Study were published, maternal-fetal surgery for the in utero treatment of spina bifida has become accepted as a standard of care alternative. Despite promise with fetal management of myelomeningocele repair, there are significant complications to consider. Chorioamniotic membrane separation and preterm premature rupture of membranes are known complications of invasive fetal procedures. Despite their relative frequency associated with fetal procedures, few data exist regarding risk factors that may be attributed to their occurrence or the natural history of pregnancies that are affected with chorionic membrane separation or preterm premature rupture of membranes related to the procedure. OBJECTIVE: The objective of this study was to review chorioamniotic membrane separation and preterm premature rupture of membranes in a cohort of patients undergoing fetal management of myelomeningocele repair including identification of risk factors and outcomes. STUDY DESIGN: This was a retrospective review of patients undergoing fetal management of myelomeningocele repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fetal management of myelomeningocele repair database and chart review was performed. Perioperative factors and outcomes among patients with chorioamniotic membrane separation and preterm premature rupture of membranes were compared to those without. Risk factors associated with the development of chorioamniotic membrane separation and preterm premature rupture of membranes were determined. RESULTS: A total of 88 patients underwent fetal management of myelomeningocele repair and subsequently delivered during the study period. In all, 21 patients (23.9%) were diagnosed with chorioamniotic membrane separation by ultrasound and preterm premature rupture of membranes occurred in 27 (30.7%). Among the chorioamniotic membrane separation patients, 10 (47.6%) were diagnosed with global chorioamniotic membrane separation and 11 (52.4%) with local chorioamniotic membrane separation. Earlier gestational age at the time of fetal surgery was a significant risk factor for the development of chorioamniotic membrane separation (P = .01) and preterm premature rupture of membranes (P < 0.0001). Chorioamniotic membrane separation was significantly associated with preterm premature rupture of membranes (59.1% vs 21.2%, P = .008) and earlier gestational age at delivery (32.1 ± 4.2 vs 34.4 ± 3.5 weeks, P = .01). The average number of days from chorioamniotic membrane separation to preterm premature rupture of membranes was 11.0 ± 10.1 and from chorioamniotic membrane separation to delivery was 31.0 ± 22.5. The mean time interval between fetal management of myelomeningocele repair and preterm premature rupture of membranes was 47.9 days. Mean latency period from preterm premature rupture of membranes to delivery was 25 days. Gestational age at delivery was significantly lower in patients with preterm premature rupture of membranes (31.6 ± 3.4 vs 34.9 ± 3.5 weeks, P = .0001). Using logistic regression analysis, nulliparity, gestational age at fetal management of myelomeningocele repair, and membrane separation remained significant risk factors for preterm premature rupture of membranes. CONCLUSION: Chorioamniotic membrane separation after fetal management of myelomeningocele repair is a significant risk factor for subsequent development of preterm premature rupture of membranes and preterm delivery. Fetal management of myelomeningocele repair <23 weeks is associated with higher rates of preterm premature rupture of membranes and chorioamniotic membrane separation. Therefore fetal management of myelomeningocele repair should be deferred until ≥23 weeks to mitigate these complications. Nulliparity also appears to increase the risk for preterm premature rupture of membranes.

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.

Thoracoamniotic shunts for the management of fetal lung lesions and pleural effusions: a single-institution review and predictors of survival in 75 cases.

PURPOSE: Hydrops and pulmonary hypoplasia are associated with significant morbidity and mortality in the setting of a congenital lung lesion or pleural effusion (PE). We reviewed our experience using in utero thoracoamniotic shunts (TA) to manage fetuses with these diagnoses. METHODS: A retrospective review of fetuses diagnosed with a congenital lung lesion or pleural effusion who underwent TA shunt placement from 1998-2013 was performed. RESULTS: Ninety-seven shunts were placed in 75 fetuses. Average gestational age (±SD) at shunt placement and birth was 25±3 and 34±5 weeks. Shunt placement resulted in a 55±21% decrease in macrocystic lung lesion volume and complete or partial drainage of the PE in 29% and 71% of fetuses. 69% of fetuses presented with hydrops, which resolved following shunt placement in 83%. Survival was 68%, which correlated with GA at birth, % reduction in lesion size, unilateral pleural effusions, and hydrops resolution. Surviving infants had prolonged NICU courses and often required either surgical resection or tube thoracostomy in the perinatal period. CONCLUSION: TA shunts provide a therapeutic option for select fetuses with large macrocystic lung lesions or PEs at risk for hydrops and/or pulmonary hypoplasia. Survival following shunting depends on GA at birth, reduction in mass size, and hydrops resolution.

Diagnosis of 9q22.3 microdeletion syndrome in utero following identification of craniosynostosis, overgrowth, and skeletal anomalies.

9q22.3 microdeletion syndrome is a well-described contiguous deletion syndrome with features of Gorlin syndrome and other manifestations. Commonly reported findings in addition to those of Gorlin syndrome include metopic craniosynostosis, hydrocephalus, intellectual disability, and minor facial anomalies. The critical region for this condition was found to include the PTCH1 and FANCC genes; however, other genes are often deleted in affected individuals but their role in the observed phenotype is not understood. Fewer than 50 individuals with 9q22.3 microdeletion have been reported, all diagnosed postnatally on the basis of the phenotype. A confirmed prenatal diagnosis and accompanying fetal imaging has not been reported to date. We describe a patient with prenatally diagnosed 9q22.3 microdeletion syndrome following the ultrasonographic identification of trigonocephaly, macrosomia, organomegaly, ventriculomegaly, and anomalous vertebrae.

Fetal myelomeningocele repair: the post-MOMS experience at the Children's Hospital of Philadelphia.

BACKGROUND: Fetal myelomeningocele (fMMC) repair has become accepted as a standard of care option in selected circumstances. We reviewed our outcomes for fMMC repair from referral and evaluation through surgery, delivery and neonatal discharge. MATERIAL AND METHODS: All patients referred for potential fMMC repair were reviewed from January 1, 2011 through March 7, 2014. Maternal and neonatal data were collected on the 100 patients who underwent surgery. RESULTS: 29% of those evaluated met the criteria and underwent fMMC repair (100 cases). The average gestational age was 21.9 weeks at evaluation and 23.4 weeks at fMMC repair. Complications included membrane separation (22.9%), preterm premature rupture of membranes (32.3%) and preterm labor (37.5%). Average gestational age at delivery was 34.3 weeks and 54.2% delivered at ≥35 weeks. The perinatal loss rate was 6.1% (2 intrauterine fetal demises and 4 neonatal demises); 90.8% of women delivered at the Children's Hospital of Philadelphia and 3.4% received transfusions. With regard to the neonates, 2 received ventriculoperitoneal shunts prior to discharge; 71.1% of neonates had no evidence of hindbrain herniation on MRI. Of the 80 neonates evaluated, 55% were assigned a functional level of one or more better than the prenatal anatomic level. CONCLUSION: In an experienced program, maternal and neonatal outcomes for patients undergoing fMMC repair are comparable to results of the MOMS trial.

The role of echocardiography in the intraoperative management of the fetus undergoing myelomeningocele repair.

INTRODUCTION: Fetal surgery for myelomeningocele (MMC) results in better outcomes compared to postnatal treatment. However, risks are present. We describe our experience with intraoperative fetal echocardiography during repair of MMC and report on the management of serious cardiovascular events. MATERIAL AND METHODS: The subjects included fetuses with intent to repair MMC from January 2011 to February 2014. The protocol involved continuous echocardiography in a looping, sequential manner of systolic function, heart rate and tricuspid and mitral valve regurgitation. RESULTS: A total of 101 cases intended fetal MMC repair; 100 completed surgery. Intraoperative ventricular dysfunction was present in 60% (20 mild, 25 moderate, 15 severe). Heart rate <100 bpm was noted in 11 cases. Tricuspid valve regurgitation was present in 35% (26 mild, 7 moderate, 2 severe); mitral valve regurgitation was present in 19% (15 mild, 4 moderate). Serious cardiovascular events were experienced in 7 cases, which affected the conduct of surgery and/or outcome. In 4 of these, medications were given via the umbilical vein and external cardiac compressions were performed. Fetal echocardiography was used to gauge the efficacy of compressions and to guide resuscitation. DISCUSSION: Cardiovascular compromise is common during fetal surgery for MMC. Intraoperative fetal echocardiography is recommended as a growing number of centers contemplate offering this form of novel, but potentially risky, therapy.

Open fetal surgery for central bronchial atresia.

Mainstem or lobar bronchial atresia is associated with massive pulmonary hyperplasia, contralateral pulmonary hypoplasia, non-immune hydrops and a fatal fetal prognosis. Open fetal surgery currently provides a potential therapeutic option for management of a fetus with this diagnosis. We present 2 cases of open fetal surgery for bronchial atresia at the level of the mainstem and lobar bronchus. The first case involved a left pneumonectomy performed at 26 weeks' gestation. After successful intraoperative resuscitation for fetal cardiac arrest, the fetus survived until 32 weeks' gestation when preterm premature rupture of membranes prompted delivery. The neonate expired on day of life (DOL)1. The second case involved a left upper lobectomy performed at 24(3)/7 weeks' gestation. The fetus was delivered at 34(3)/7 weeks' gestation and, after a prolonged NICU course including a completion pneumonectomy and tracheostomy, was discharged home at 8 months of life. This second case is the first report of survival following open fetal surgery for central bronchial atresia. This report highlights the potential benefit of fetal lung resection for central bronchial atresia while describing the many challenges to achieve the successful management of a fetus with this condition.