Faculty Bibliography

INTRODUCTION/BACKGROUND:Fetal endoscopic tracheal occlusion in congenital diaphragmatic hernia (CDH) may reduce pulmonary hypertension and ameliorate postnatal cardiac output. The effects of sustained early (ETO) and late (LTO) tracheal occlusion on left ventricular (LV) cells in the lamb model have not been described. MATERIALS AND METHODS/METHODS:CDH was created in lambs at 70 days' gestation (term = 145 days). ETO (85 days) or LTO (105 days) was sustained till term. After cesarean section (140 days) fetuses were euthanized and hearts harvested. LV myocardial cells were studied by histological and immunofluorescence (TGF-beta 1, endothelin-1) assays in CDH, ETO, LTO, and the control group (two subjects per group). Small intramyocardial arteries were evaluated by traditional histology. RESULTS:LV myocardial histology in CDH and LTO was similar. ETO-induced LV myocardial cell enlargement and increased endothelin-1 and TGF-beta 1 staining; a weaker immunofluorescence signal was observed in LTO compared with ETO. Myocardial vascular wall thickness was greater in CDH than in controls. ETO was associated with a vascular wall thickness within the range of controls. CONCLUSION/CONCLUSIONS:With only two fetuses in each group, only an explorative evaluation was possible. The time point at which TO is performed seems to have an effect on cardiac morphology. Functional studies as well as confirmation in clinical samples are mandatory.

INTRODUCTION/BACKGROUND:The lung-to-head ratio (LHR) is routinely used to select the best candidates for prenatal surgery and to follow-up the fetuses with congenital diaphragmatic hernia (CDH). Since this index is gestation-dependent, the quantitative lung index (QLI) was proposed as an alternative parameter that stays constant throughout pregnancy. Our objective was to study the performance of QLI to predict survival in fetuses with CDH. MATERIALS AND METHODS/METHODS:Observational retrospective study of fetuses with isolated CDH, referred to our center. LHR was originally used for the prenatal surgery evaluation. We calculated the QLI and compared the performance of both indexes (QLI and LHR) to predict survival. RESULTS:From January-2009 to February-2015 we followed 31 fetuses with isolated CDH. The mean QLI was 0.66 (95% CI: 0.57-0.75) for survivors and 0.41 (95% CI: 0.25-0.58) for non-survivors (p<0.01) and the mean LHR was 1.38 (95% CI: 1.17-1.60) for survivors and 0.91 (95% CI: 0.57-1.25) for non-survivors (p<0.02). All operated fetuses (n=12) had a LHR <1 and a QLI <0.5 and none of them survived when the QLI was <0.32. When separately considering the prenatal surgery status, the mean values of the QLI (but not those of the LHR) were still significantly different between survivors and non-survivors. The comparative ROC curves showed a better performance of the QLI with respect to the LHR for the prediction of survival, especially in the group of operated fetuses, although differences were not statistically significant. COMMENT/CONCLUSIONS:The QLI seems to be a better predictor for survival than the LHR, especially for the group of fetuses undergoing prenatal surgery.

Persistent cloaca malformation is the most severe type of anorectal and urogenital malformation. Decisions concerning the surgical treatment for this condition are taken during the first hours of life and may determine the quality of life of these patients. Thus, prenatal diagnosis becomes important for a prompt and efficient management of the fetus and newborn, and accurate counseling of the parents regarding its consequences and the future of the baby. Careful evaluation by ultrasonography, and further in-depth analysis with MRI, allow prenatal detection of characteristic findings, which can lead to diagnose or at least suspect this condition. We reviewed our experience and the literature in order to highlight the most important clues that can guide the physician in the differential diagnosis.

Fetal teratomas are the most common tumors diagnosed prenatally. The majority of these tumors are benign and cured by complete resection of the mass during the neonatal period. Prenatal diagnosis has improved the perinatal management of these lesions and especially for the teratomas that might benefit from fetal intervention. A comprehensive prenatal evaluation including conventional ultrasounds, Doppler, echocardiography and fetal MRI, is essential for an effective counseling and perinatal management. Antenatal counseling helps the parents to better understand the natural history, fetal intervention, and perinatal management of these tumors, which differ dramatically depending on their size and location. Fetal surgical debulking improves survival in cases of sacrococcygeal teratoma with cardiac decompensation. Additionally, the use of an EXIT procedure reduces the morbidity and mortality if a complicated delivery in cases of cervical and mediastinal teratomas. Here, we offer an overview of all fetal teratomas and their recommended management, with emphasis on in utero treatment options.

BACKGROUND:Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension. Tracheal occlusion (TO) stimulates fetal lung growth and maturation and reverse vascular changes responsible for pulmonary hypertension, which are related to mechanisms involving nitric oxide (NO) in CDH. We aim to evaluate the effect of TO and ventilation on NO pathways. METHODS:Eight groups were created: (1) control; (2) control ventilated (CV); (3) CDH (CDH); (4) CDH ventilated (CDHV); (5) TO control; (6) TO ventilated; (7) TO + CDH; and (8) TO + CDH ventilated (CDHTOV). Fetuses were weighed, and volume ventilated for 30 min after harvested. Total lung weight and the ratio of total lung weight to body weight, thickness of the middle layer of the pulmonary arteriole, and the air space diameter were measured. The NO synthase inducible and NO synthase inducible were performed by immunohistochemistry and Western blotting. RESULTS:The total lung weight and the ratio of total lung weight to body weight decreased in animals with nitrofen and also after ventilation for all groups (P < 0.05). The thickness of the middle layer of the pulmonary arteriole decreased in all groups with TO when compared with controls (P < 0.001). The air space diameter decreased after ventilation in the CDHTOV compared to the TO + nitrofen-induced CDH (P < 0.001). Compared to nonventilated cohorts, NO synthase inducible increased in CV and TO ventilated (P < 0.001) and decreased in CDHV and CDHTOV (P < 0.001). NO synthase inducible increased in CV and CDHV (P < 0.001) and decreased in the TO control and CDHTOV (P < 0.001). CONCLUSIONS:TO and ventilation alter the NO pathway with possible implications in reducing the pulmonary hypertension in CDH.

OBJECTIVE:The purpose of this study is to identify differences in findings between open and closed spinal dysraphisms seen on fetal MR images. MATERIALS AND METHODS/METHODS:A single-institution retrospective analysis of fetal MR images for spinal dysraphism was performed. Postnatal images and clinical and operative reports were reviewed. RESULTS:Sixteen fetuses with postnatally confirmed closed spinal dysraphisms were included. Of these, 25% (4/16) had posterior fossa anomalies, 12.5% (2/16) had ventriculomegaly, and 37.5% (6/16) had OEIS (omphalocele, exstrophy, imperforate anus, and spinal defects) complex. Of 90 fetuses with postnatally confirmed open spinal dysraphism, 95.6% (86/90) had posterior fossa anomalies, 85.6% (77/90) had ventriculomegaly, and none had OEIS complex. Twenty fetuses with open spinal dysraphism were randomly selected to compare with fetuses with closed spinal dysraphisms. Continuity of the epidermal and subcutaneous tissues with the sac wall on fetal MR images was seen in 93.8% (15/16) of patients with closed spinal dysraphisms, as opposed to 5% (1/20) of patients with open spinal dysraphisms. The mean (± SD) sac wall thickness was less in open (0.7 ± 0.6 mm) than closed (2.9 ± 1.3 mm; p < 0.001) spinal dysraphism. None of the fetuses had T1-hyperintense fat within the defect. CONCLUSION/CONCLUSIONS:On fetal MR images, closed spinal dysraphisms tend to have a sac wall in continuity with the epidermal and subcutaneous tissues, a thicker sac wall, fewer posterior fossa anomalies, and high association with OEIS complex.

OBJECTIVE:The aim of this study was to determine whether fetal lung volume and visceral herniation are associated with changes in intrathoracic space in congenital diaphragmatic hernia(CDH). METHODS:We retrospectively examined the relationship between magnetic resonance imaging-derived measurements of intrathoracic space [predicted lung volume (PLV)] and residual lung volume or visceral herniation among isolated left-sided CDH fetuses. RESULTS:Data from fetal magnetic resonance imaging studies of 60 isolated left-sided CDH cases were analyzed. The median PLV of the CDH fetuses was found to be much greater than the expected total lung volume (eTLV) of a normal fetus at the same gestational age. Surprisingly, liver herniation and observed TLV(oTLV) were positively correlated with the PLV. Although the PPLV was consistently less than the o/eTLV, both indices were greater in survivors than in non-survivors, whereas no significant difference was seen in the PLV/eTLV ratio in regard to survivorship. CONCLUSION/CONCLUSIONS:The intrathoracic domain available for lungs and viscera is expanded in CDH fetuses and positively affected by the lung volume and the presence of liver herniation, leading to the difference in the PPLV and o/eTLV. Future study of intrathoracic space as it relates to the growth of the lung and herniated viscera is needed to better characterize the relationship between these parameters.

Fetal endoscopic tracheal occlusion has been proposed as a prenatal intervention to ameliorate congenital diaphragmatic hernia (CDH) prognosis. Tracheal occlusion (TO) prevents pulmonary fluid egress, leading to tissue expansion, reversal of lung hypoplasia, and potential maturation. Fetal lung maturity strongly correlates with amniotic fluid (AF) phospholipidic composition. In this preliminary study, we characterized the AF phospholipidic profile in CDH-induced, TO-treated, and healthy fetal lambs to define the prenatal treatment benefits of TO on lung maturity. CDH induction was performed at 70 days of gestation, TO was carried out at 102 days of gestation, and caesarean section was carried out at 136 days of gestation. AF samples, taken at 102-136 days of gestation, were evaluated using mass spectrometry. The analysis focused on phosphatidylcholines (PCs) and sphingomyelins (SMs). The most abundant phosphatidylcholine species retrieved in healthy AF was POPC [PC(18:1/16:0)], while the level of DPPC [PC(16:0/16:0)] was extremely low at both gestational ages. CDH induction caused a decrease in POPC and many other PCs. A substantial return of some PCs, in particular POPC, PC(34:2) and PC(18:0/16:0), to a more physiological level was prompted by TO. SMs were unaltered. The AF phospholipidic profile could provide prenatal prognostic markers of CDH and possible indices of lung maturation after fetal treatment.

Progress in the last three decades in prenatal genetic diagnosis and advancement in prenatal imaging and characterization of fetal anomalies have allowed better preparation in family counseling and afforded the opportunity to consider prenatal treatment for congenital defects that would have fatal outcomes, among them the fetal tumors. Advances in fetal therapy and surgical approaches including minimally invasive procedures, have permitted not just the survival of rare tumor cases but improved long-term outcomes. In this review, we described some of the most common fetal tumors and their recommended management with emphasis on in utero treatment options.

OBJECTIVE:The aim of this research was to compare the impact of varying degrees of visceral herniation on the growth rates of the contralateral and ipsilateral fetal lungs in cases of isolated left-sided congenital diaphragmatic hernia (CDH). METHODS:Data were retrieved from 58 fetuses with isolated left-sided CDH undergoing magnetic resonance imaging studies at both mid-gestation (20-30 weeks) and late-gestation (>30 weeks) time points. The growth of the right and left lungs (ΔLV-R and ΔLV-L) was calculated. The impact of the degree of visceral herniation on the growth disparity between the right and left lungs was then compared. RESULTS:Measurable growth occurred in both lungs between the mid-gestation and late-gestation time points in each group. The ΔLV-R exhibited a strong correlation with ΔLV-L. However, the right lung grew significantly faster than the left lung (ΔLV-R = 1.36 vs ΔLV-L = 0.17 mL/week, P < 0.001). A higher degree of visceral herniation appeared to decrease the growth rate disparity by progressive limitation of the growth of the right lung. CONCLUSION/CONCLUSIONS:The contralateral lung retains the potential to grow faster than the ipsilateral lung during the third trimester. A higher degree of visceral herniation places progressive limitations on contralateral lung growth thereby diminishing the growth rate disparity between the right and left lungs.