Faculty Bibliography

OBJECTIVES/OBJECTIVE:Congenital high airway obstruction syndrome (CHAOS) is characterized by over-distended lungs leading to impaired cardiac return and fetal hydrops. Survivors have been reported following prenatal spontaneous fistulization, fetal procedures to decompress the airway, or ex-utero intrapartum treatment (EXIT). The long-term outcomes of survivors are unclear. METHODS:We performed a retrospective chart review on patients diagnosed with CHAOS in our center between 2005-2025. RESULTS:Of the 28 patients with CHAOS, three (10.7%) underwent a fetal procedure to decompress the airway. Three patients (10.7%) had evidence of spontaneous fistulization. Four patients (14.3%) terminated the pregnancy and four (14.3%) had in-utero fetal demise. Twenty patients (71.4%) were live-born; of these, 14 (70%) died shortly after delivery and two (10%) died in the neonatal period. Seven patients (35%) underwent EXIT-to-tracheostomy at our center, of which four (57.1%) are long-term survivors ranging in age from 4 to 19 years old. Three patients have undergone airway reconstruction between 1.6 and 5.6 years of age; one remains tracheostomy-dependent due to recurrent airway stenosis, one patient has undergone reconstruction and is likely to be decannulated soon, and one patient had successful reconstruction and was decannulated. The fourth patient has not yet undergone airway reconstruction. CONCLUSIONS:CHAOS remains a highly morbid diagnosis, but long-term survivorship and liberation from tracheostomy is possible.

OBJECTIVE:Infants with myelomeningocele (MMC) are at risk of brainstem dysfunction secondary to symptomatic Chiari II malformation with hindbrain herniation (HH), which can manifest as feeding difficulties including aspiration and dysphagia. This study aims to investigate whether prenatal repair of MMC is associated with improved feeding outcomes compared to postnatal repair. STUDY DESIGN/METHODS:Retrospective observational study of 208 infants with MMC, 105 repaired prenatally and 103 repaired postnatally, from January 2011 to July 2022. Primary outcome was feeding tube at discharge and longitudinally through 12 months corrected gestational age (CGA). RESULTS:9.5% of infants repaired prenatally and 13.6% repaired postnatally required feeding tube at discharge (p = 0.3585). By 53 weeks CGA, the prenatal repair group had decreased odds of requiring feeding tube (0.325 [95% CI 0.121, 0.872]). CONCLUSION/CONCLUSIONS:Prenatal MMC repair was associated with decreased need for long-term feeding support, suggesting a potential functional benefit of prenatal repair related to reversal of HH.

OBJECTIVE:To compare postnatal MRI outcomes after prenatal myelomeningocele repair using three different dural substitutes. METHOD/METHODS:32 sheep fetuses were included, with 34.3%(11/32) serving as healthy controls and the remaining undergoing prenatal spinal lumbar defect creation to recreate a myelomeningocele in the fetus. 90.5% (19/21) of sheep fetuses with surgically created MMC underwent repair using traditional collagen (Durapair) patch (n = 6), HUC matrix (NEOX RT) patch (n = 6), or a novel PLA/PCL patch (n = 7). All sheep underwent brain and spine MRI within 24 h after delivery. Images were reviewed in Research PACS by a pediatric neuroradiologist and were assessed for ventricle size, degree of hindbrain herniation, spinal cord integrity, and fluid collection at the repair site. RESULTS:There was a significant reduction in hindbrain herniation in all three intervention groups when compared with MMC without prenatal intervention. There was increased incidence of complete spinal cord defect (3/7), pseudomeningocele (5/7) and intraspinal cyst (2/7) at the repair site of the PLA/PCL patch compared with the Durapair and NEOX RT patches. CONCLUSIONS:This study demonstrates equal efficacy in reducing hindbrain herniation in MMC repair by Durapair, NEOX RT, and PLA/PCL patches by MRI. Future studies analyzing the interaction of the patches with the host tissue in animal models and clinical trials will help to better determine the true safety and efficacy of these novel patches for clinical use.

OBJECTIVE:Amnioinfusions in anhydramnios aim to promote fetal lung development, but currently used fluids (Normal Saline [NS], Lactated Ringer's [LR]) fail to mimic the intrauterine environment and increase reactive oxygen species (ROS). We developed a synthetic amniotic fluid (Amnio-well, AW) designed to reduce intrauterine ROS. This study evaluated the pulmonary and gastrointestinal effects of 2 formulations of AW compared with those of NS and LR in a pre-clinical model. METHOD:At gestational age E17.5, pregnant rats underwent amniotic fluid replacement with NS, LR, AW, AW plus epidermal growth factor and transforming growth factor-β (AW++), or sham control. Fetal lungs were harvested at E20.5 for histology, fractional airspace, and blinded pathological evaluation. Surfactant protein (SP-A, SP-B, SP-C) expression and inflammatory gene panels were assessed in lungs and gastrointestinal (GI) tissue. RESULTS:NS and LR lungs demonstrated edema, macrophage infiltration, and reduced airspace (p < 0.001). AW improved SP-B and SP-C relative to control, whereas AW++ suppressed SP-B and SP-C (p < 0.05). Lung gene profiling showed NS/LR induced alterations in histamines, annexins, and immune recruitment, while AW closely resembled control. GI histology was similar across groups, though NS/LR altered TNF, prostaglandin, and adhesion pathways (p < 0.05). CONCLUSION:AW reduced lung inflammation and enhanced surfactant expression compared with NS or LR, with minimal GI effects.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Congenital obstructive hydrocephalus (HCP) causes progressive, irreversible fetal brain damage through ventricular enlargement and increasing fetal cerebral tissue compression. Postnatal treatments of choice include ventriculoperitoneal shunting or endoscopic third ventriculostomy (ETV). Intrauterine treatments, such as ventriculoamniotic shunting, were attempted unsuccessfully 4 decades ago and failed to improve postnatal outcomes, likely due to inadequate fetal patient selection. The aim of this study was to evaluate the efficacy of prenatal ETV for early ventricular decompression and potential prevention of fetal brain damage in hydrocephalic fetal lambs. METHODS:HCP was induced in 24 fetal lambs by injecting BioGlue into the cisterna magna at E85. Three weeks later (E105-110), fetal ETV was successfully performed on 8 fetuses using a small rigid cystoscope. Fetal brain lateral ventricular diameters and cerebral mantle thicknesses were monitored by prenatal and postnatal ultrasounds and fetal MRI. RESULTS:According to the Cincinnati HCP Severity Scale, moderate and severe HCP subgroups responded positively to fetal ETV with reduced cerebral ventricular diameters. Ten days post-ETV, severe HCP fetal lambs improved to moderate levels, whereas those with moderate HCP normalized by birth. A similar improvement pattern was seen for the mechanical compression threshold (ventricular diameters/biparietal diameter). Biparietal diameter values did not significantly differ among nontreated, treated, and normal control groups during pregnancy. MRI revealed a significant increase in brain mantle thickness in the prenatally treated fetuses. CONCLUSION/CONCLUSIONS:Prenatal ETV is feasible in hydrocephalic fetal lambs and effectively reverses ventriculomegaly and brain compression in cases of severe or moderate fetal HCP in this ovine model.

Congenital diaphragmatic hernia (CDH) is characterized by pulmonary hypoplasia and vascular underdevelopment, leading to impaired gas exchange and high neonatal mortality. Accurate and quantitative assessment of pulmonary vasculature is crucial for understanding disease severity, but manual segmentation of three-dimensional vascular networks in medical images is time-consuming and operator-dependent. This protocol presents a fully automated deep learning-based method for pulmonary vessel segmentation and morphometric analysis using postnatal computed tomography (CT) scans. The pipeline includes standardized preprocessing steps - conversion to Hounsfield units, windowing, isotropic resampling, and contrast-limited adaptive histogram equalization (CLAHE) - to normalize imaging data and enhance vascular visibility. A U-Net convolutional neural network (CNN) architecture is then trained to segment the pulmonary vasculature, followed by a three-dimensional skeletonization algorithm to quantify morphometric parameters such as branch number, mean branch length, and generational depth. Representative results demonstrate that the proposed model achieves high segmentation accuracy, with the transfer learning configuration yielding the best performance. Quantitative morphometric analysis reveals markedly reduced vascular complexity in CDH compared with control lungs, consistent with the known pathological features of pulmonary hypoplasia. This automated approach enables reproducible, quantitative, and non-invasive evaluation of pulmonary vascular morphology in CDH. The method can be adapted to other imaging modalities and applied to studies of fetal and neonatal lung development, facilitating translational research and future clinical integration.

Congenital diaphragmatic hernia (CDH) is a severe congenital malformation resulting from incomplete diaphragm development, leading to abdominal organ herniation into the thoracic cavity. This disruption compromises pulmonary development, frequently resulting in lung hypoplasia and pulmonary hypertension. While the role of the placenta in congenital heart defects is well established, its involvement in congenital lung diseases, particularly CDH, remains unexplored. During the prenatal period, the placenta serves as a crucial site for nutrient and gas exchange between the mother and the fetus, and given its functional connection to fetal development, it provides a compelling avenue for investigating the pathophysiology of CDH. This review synthesizes current knowledge regarding the placental contribution to CDH, with a focus on molecular pathways, particularly the retinoic acid pathway and placental abnormalities. Evidence from both animal models and human studies suggests a complex interplay between placental function and CDH pathogenesis. Further investigation is required to elucidate the placenta's role in disease mechanisms, which may offer perspectives for future research, advances in prenatal diagnostics, and therapeutic strategies.

BACKGROUND/OBJECTIVES/OBJECTIVE:Gastroschisis remains one of the most debated congenital abdominal wall defects with respect to its embryologic and developmental origins. Despite decades of investigation, no consensus exists regarding a single causative mechanism, and competing hypotheses variably explain laterality, bowel injury, and closing variants. This scoping review aims to synthesize historical and contemporary embryologic theories of gastroschisis and integrate them into a coherent developmental framework with direct relevance to prenatal assessment and clinical interpretation. METHODS:A structured literature search was conducted in PubMed, Web of Science, and Scopus from inception through December 2025. Studies proposing original embryologic mechanisms or providing primary experimental, placental, or developmental evidence were included. Eligible publications were qualitatively synthesized and classified according to evidence strength as historical descriptive, experimental, placental pathology, or integrative synthesis. Embryologic theories were organized into mechanistic categories based on affected structures, developmental timing, and proposed pathophysiology. RESULTS:Twenty-six publications met inclusion criteria, yielding fourteen distinct embryologic theories. These were categorized into four mechanistic categories: mesodermal and ventral body wall folding abnormalities, vascular disruption models, umbilical ring and extraembryonic attachment defects, and integrated multifactorial developmental concepts. No single mechanistic category alone consistently accounted for right-sided predominance, variability in bowel injury, and the occurrence of closing variants. CONCLUSIONS:Gastroschisis is best understood as a spectrum of periumbilical developmental disturbances arising from interacting mesodermal, vascular, and biomechanical factors. An integrated embryologic framework improves interpretation of dynamic prenatal imaging findings, supports refined risk stratification and counseling, and provides a biologic foundation for future translational research.