Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study.

BACKGROUND: Congenital diaphragmatic hernia (CDH) accounts for 8% of all major congenital anomalies. Neonates who are small for gestational age (SGA) generally have a poorer prognosis. We sought to identify risk factors and variables associated with outcomes in neonates with CDH who are SGA in comparison to neonates who are appropriate for gestational age (AGA). METHODS: We used the multicenter Diaphragmatic Hernia Research & Exploration Advancing Molecular Science (DHREAMS) study to include neonates enrolled from 2005 to 2019. Chi-squared or Fisher's exact tests were used to compare categorical variables and t tests or Wilcoxon rank sum for continuous variables. Cox model analyzed time to event outcomes and logistic regression analyzed binary outcomes. RESULTS: 589 neonates were examined. Ninety were SGA (15.3%). SGA patients were more likely to be female (p = 0.003), have a left sided CDH (p = 0.05), have additional congenital anomalies and be diagnosed with a genetic syndrome (p < 0.001). On initial single-variable analysis, SGA correlated with higher frequency of death prior to discharge (p < 0.001) and supplemental oxygen requirement at 28 days (p = 0.005). Twice as many SGA patients died before repair (12.2% vs 6.4%, p = 0.04). Using unadjusted Cox model, the risk of death prior to discharge among SGA patients was 1.57 times the risk for AGA patients (p = 0.029). There was no correlation between SGA and need for ECMO, pulmonary hypertensive medication at discharge or oxygen at discharge. After adjusting for confounding variables, SGA no longer correlated with mortality prior to discharge or incidence of unrepaired defects but remained significant for oxygen requirement at 28 days (p = 0.03). CONCLUSION: Infants with CDH who are SGA have worse survival and poorer lung function than AGA infants. However, the outcome of SGA neonates is impacted by other factors including gestational age, genetic syndromes, and particularly congenital anomalies that contribute heavily to their poorer prognosis.

Standardization of amniotic fluid leptin levels and utility in maternal overweight and fetal undergrowth.

OBJECTIVE: Leptin is an adipokine that regulates energy homeostasis. The objective of this study was to establish a gestational age-specific standard for amniotic fluid leptin (AFL) levels and examine the relationship between AFL, maternal overweight and fetal growth restriction. STUDY DESIGN: Amniotic fluid was obtained at mid-gestation from singleton gravidas, and leptin was quantified using enzyme-linked immunosorbent assay. Amniotic fluid samples from 321 term pregnancies were analyzed. Clinical data, including fetal ultrasound measurements and maternal and infant characteristics, were available for a subset of patients (n=45). RESULTS: The median interquartile range AFL level was significantly higher at 14 weeks' gestation (2133 pg ml(-1) (1703 to 4347)) than after 33 weeks' gestation (519 pg ml(-1) (380 to 761), P trend<0.0001), an average difference of 102 pg ml(-1) per week. AFL levels were positively correlated with maternal pre-pregnancy body mass index (BMI) (r=0.36, P=0.03) adjusting for gestational age at measurement, but were not associated with fetal growth. CONCLUSIONS: AFL levels are higher at mid-gestation than at late gestation, and are associated with maternal pre-pregnancy BMI.

Regulation of amino acid transporters by adenoviral-mediated human insulin-like growth factor-1 in a mouse model of placental insufficiency in vivo and the human trophoblast line BeWo in vitro.

Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor-11 (hIGF-1) in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined amino acid transporter expression and localization in both a mouse model of placental Insufficiency (PI) and a model of human trophoblast, the BeWo Choriocarcinoma cell line. For in vitro human studies, BeWo Choriocarcinoma cells were maintained in F12 complete medium + 10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 h. MOIs of 10:1 and 100:1 were utilized. In BeWo, transfection efficiency was 100% at an MOI of 100:1 and Ad-IGF-1 significantly increased IGF-1 secretion, proliferation and invasion but reduced apoptosis compared to controls. In vitro, amino acid uptake was increased following Ad-IGF-1 treatment and associated with significantly increased RNA expression of SNAT1, 2, LAT1 and 4F2hc. Only SNAT2 protein expression was increased but LAT1 showed relocalization from a perinuclear location to the cytoplasm and cell membrane. For in vivo studies, timed-pregnant animals were divided into four groups on day 18; sham-operated controls, uterine artery branch ligation (UABL), UABL + Ad-hIGF-1 (10(8) PFU), UABL + Ad-LacZ (10(8) PFU). At gestational day 20, pups and placentas were harvested by C-section. Only LAT1 mRNA expression changed, showing that a reduced expression of the transporter levels in the PI model could be partially rectified with Ad-hIGF1 treatment. At the protein level, System L was reduced in PI but remained at control levels following Ad-hIGF1. The System A isoforms were differentially regulated with SNAT2 expression diminished but SNAT1 increased in PI and Ad-hIGF1 groups. Enhanced amino acid isoform transporter expression and relocalization to the membrane may be an important mechanism contributing to Ad-hIGF-1 mediated correction of placental insufficiency.

Recapitulation of characteristics of human placental vascular insufficiency in a novel mouse model.

OBJECTIVE: We tested the effects of selective reduction of placental blood flow by mesenteric uterine artery branch ligation (MUAL) resulting in fetal growth restriction (FGR). METHODS: Timed mated C57BL/6J Day(D) 18 dams were divided into two groups: MUAL (n = 18); and control-sham (n = 18). Pups were delivered on D20, cross-fostered to surrogate CD-1 mothers for 4 weeks, and followed for 8 weeks. Outcome data included birth and placental weight, postnatal growth, placental volume determined by stereology, quantification of placental insulin-like growth factors-1(IGF-1) and IGF-2 and IGF binding proteins(IGFBP 2 and 6) by ELISA and gene expression by qPCR and GeneChip microarray analysis. RESULTS: Compared with control, MUAL had an 11% reduction in mean birth weight (1.06 ± 0.13 g vs. 0.94 ± 0.13 g, p < 0.001) but no difference in placental weight. At 4 weeks of age, mean body weights of MUAL pups were significantly lower than sham. By 8 weeks, males but not females MUAL mice achieved equivalent mean body weight to control. Placental labyrinth depth, volume, and placental gene expression of IGF-1 and 2 were significantly reduced by MUAL. In contrast, placental protein level of IGFBP-2 and 6 were significantly elevated in the MUAL. Genomic expression analysis demonstrated that MUAL pups significantly up-regulated genes that were associated with apoptosis and growth pathways. CONCLUSION: This novel mouse animal model of FGR using selective ligation recapitulates multiple characteristics of placental vascular insufficiency (PI) in humans. This is the first non-genetic mouse model of PI which offers its application in transgenic mice to better study the underlying mechanisms in PI. CONDENSATION: A new mouse model of placental vascular insufficiency by selective ligation of mesenteric uterine artery branch recapitulates multiple findings observed in human placental vascular insufficiency.

Estimated cardiac output and cardiovascular profile score in fetuses with high cardiac output lesions.

OBJECTIVE: High cardiac output lesions are associated with an increased risk of fetal death, largely as a result of cardiac failure and hydrops fetalis. The cardiovascular profile score (CVPS) has been used to characterize cardiovascular wellbeing, and has been linked to fetal outcomes in other conditions. We aimed to test the hypothesis that elevated combined cardiac output (CCO) in fetuses with high output lesions may be associated with worsening cardiovascular status, as evidenced by a lower CVPS. METHODS: A retrospective review was performed of fetuses with high cardiac output lesions that underwent echocardiography between July 2006 and November 2010. Diagnoses included sacrococcygeal teratoma, placental chorioangioma and vein of Galen aneurysm. Fetal echocardiographic evaluation included assessment of CVPS, as well as Doppler/two-dimensional estimation of CCO, indexed to estimated fetal weight (CCOi). The relationship between CCO and CVPS was assessed. RESULTS: A total of 35 fetuses were studied: 27 had sacrococcygeal teratoma, seven had chorioangioma and one had vein of Galen aneurysm. There was a significant inverse relationship between mean logCCOi and CVPS (r2 = 0.48, P = 0.008). Of 31 patients with clinical outcome data, 10 experienced either in-utero demise or intervention; 80% of these fetuses had a CVPS of < 8. CONCLUSIONS: There is an inverse relationship between CCO and CVPS in the fetus with high cardiac output lesions. As a measure of fetal cardiovascular wellbeing in this population, the CVPS may be a useful tool for stratifying risk and for selection for intervention in these fetuses.

Prevalence and progression of recipient-twin cardiomyopathy in early-stage twin-twin transfusion syndrome.

OBJECTIVE: The management of twin-twin transfusion syndrome (TTTS) in its early stages (Quintero Stages I and II) is controversial. We describe the prevalence, severity, incidence and rate of progression of recipient-twin cardiomyopathy in Stages I and II TTTS. METHODS: Among 451 cases of TTTS evaluated between 2004 and 2009, 123 (27.3%) cases of Stages I and II were reviewed. Echocardiography was used to 'upstage' cases based on the presence or absence of mild (IIIA), moderate (IIIB), or severe (IIIC) recipient cardiomyopathy. Progression was defined by worsening in the degree of recipient-twin cardiomyopathy from initial presentation or failure to respond to amnioreduction. Outcome data included progression of recipient-twin cardiomyopathy, treatment and survival to birth. Data were compared by the chi-square, Fisher's exact test or t-test as appropriate. RESULTS: Seventy-seven of 123 (62.6%) cases were Quintero Stage I and 46/123 (37.4%) Quintero Stage II. Eighty (65.0%) were upstaged to Cincinnati Stage IIIA (n = 25), IIIB (n = 23) or IIIC (n = 32). Management included observation in 11 (8.9%), amnioreduction in 26 (21.1%), amnioreduction followed by selective fetoscopic laser photocoagulation (SFLP) in 43 (35.0%) and primary SFLP in 43 (35.0%). Of 80 cases managed by observation or amnioreduction initially, 43 (53.8%) progressed within a mean duration of 1.4 ± 1.5 weeks. The incidence of progression increased significantly as degree of recipient-twin cardiomyopathy at presentation worsened: Stage I, 9/27 (33.3%); Stage II, 8/15 (53.3%); Stage IIIA, 8/16 (50.0%); Stage IIIB, 10/10 (100%); and Stage IIIC, 8/12 (66.7%) (χ(2) = 14, P < 0.01). Overall fetal survival was 205 out of 244 (84.0%). Fetal survival with observation only was 81.8% (18/22), with amnioreduction only it was 92.3% (48/52), with initial observation or amnioreduction followed by SFLP it was 86.9% (73/84) and with primary SFLP it was 76.7% (66/86). CONCLUSION: Echocardiography demonstrates a high incidence of recipient-twin cardiomyopathy in early-stage TTTS. The more advanced the recipient-twin cardiomyopathy is, the more likely is progression to occur during observation or following amnioreduction.

Placental fetal thrombotic vasculopathy in severe congenital anomalies prompting EXIT procedure.

OBJECTIVE: The ex-utero intrapartum treatment (EXIT) procedure is used to secure fetal airway, cannulate for extracorporeal membrane oxygenation (ECMO), or resect a tumor during partial delivery in a modified cesarean section. This is a retrospective study of placental pathology from EXIT procedures. METHODS: Placental reports and glass slides from 36 placentas delivered by EXIT procedure (study group SG) and 36 placentas from pregnancies without perinatal mortality and delivered by cesarean sections and matched for gestational age were blindly reviewed. Indications for EXIT procedures were: 11 cervical teratomas, 9 diaphragmatic hernias, 4 pulmonary airway malformations, 4 micrognathias, 3 vascular malformations, 3 CHAOS, and 2 aortic stenoses. 22 clinical and 43 gross and histological placental features were compared using the analysis of variance or Yates χ(2) with Holm-Bonferroni correction, where appropriate. RESULTS: The average gestational age in the SG and the CG was 34.9 weeks. Histological features of fetal thrombotic vasculopathy were more frequently seen in the SG. Of the placental features, statistically significant differences were found in, partial fibrosis of chorionic villi (9.7 ± 7.9 vs. 6.1 ± 5.3 villi per placental section) [p = 0.035], clusters of at least 3 avascular chorionic villi (33 v. 6%) [p = 0.042], and abnormal umbilical cord insertion (8% vs. 0% (p = 0.045), in the SG and the CG respectively. CONCLUSION: To the best of our knowledge, this is the first study to describe the placentas from EXIT procedures. The presence of increased frequency of fetal thrombotic vasculopathy on histology indicates an underlying chronic and on-going stasis in fetal circulation due to the presence of conditions which were indications for the EXIT procedures. The possibility of coagulopathy should be considered in management of the fetuses and neonates undergoing EXIT procedure. Detailed examination of the placenta is of utmost importance in order to recognize and treat potentially life-threatening complications.

Contribution of magnetic resonance imaging to prenatal differential diagnosis of renal tumors: report of two cases and review of the literature.

Enlargement of a kidney on prenatal imaging is usually due to hydronephrosis or cystic renal disease, and much less often results from solid tumors such as mesoblastic nephroma, Wilms' tumor, nephroblastomatosis, renal sarcoma, and angiomyolipoma. All can be diagnosed by ultrasound. Magnetic resonance imaging is useful not only in confirming the presence of a renal mass, but also in the evaluation of the contralateral kidney for subtle abnormalities. We present one case each of Wilms' tumor and mesoblastic nephroma, both detected on antenatal ultrasound and further studied with fetal magnetic resonance imaging.

TdTomato and EGFP identification in histological sections: insight and alternatives.

Tandem dimer Tomato (tdTomato) provides a useful alternative to enhanced green fluorescent protein (eGFP) for performing simultaneous detection of fluorescent protein in histological sections together with fluorescence immunohistochemistry (IHC). eGFP has many properties that make it useful for cell labeling; however, during simultaneous fluorescence IHC, the usefulness of eGFP may be limited. This limitation results from a fixation step required to identify eGFP in histological tissue sections that can mask antibody epitopes and adversely affect staining intensity. An alternative fluorescent protein, tdTomato, may assist concurrent detection of fluorescent protein within tissue sections and fluorescence IHC, because detection of tdTomato does not require tissue fixation. Tissue sections were obtained from various organs of mice ubiquitously expressing eGFP or tdTomato that were either unfixed or fixed with 4% paraformaldehyde. These tissues later were combined with fluorescence IHC. Both eGFP and tdTomato displayed robust signals in fixed frozen sections. Only tdTomato fluorescence, however, was detected in unfixed frozen sections. Simultaneous detection of fluorescence IHC and fluorescent protein in histological sections was observed only in unfixed frozen tdTomato tissue. For this reason, tdTomato is a useful substitute for eGFP for cell labeling when simultaneous fluorescence IHC is required.

Twin-reversed arterial perfusion sequence: pre- and postoperative cardiovascular findings in the 'pump' twin.

OBJECTIVES: To assess cardiovascular findings in twin-reversed arterial perfusion (TRAP) sequence pre- and post-therapy and compare these findings to traditional obstetric markers, defined as acardius to pump twin weight ratio and presence of polyhydramnios. METHODS: This was a retrospective review of 27 cases of TRAP sequence diagnosed between 2004 and 2008. Echocardiographic data included indexed cardiac output and functional and anatomic parameters. Ultrasound reports were reviewed for acardius to pump twin weight ratio and polyhydramnios. We assessed the relationship between cardiac output and the remaining cardiac/obstetric variables obtained pre- and post-treatment. RESULTS: Twenty-three subjects had complete echocardiographic data sets at initial evaluation (mean gestational age, 20.4 +/- 2.5 weeks) and, of these, post-treatment echocardiographic evaluation was available in 10. Six of seven (86%) pump twins with elevated indexed cardiac output had significant cardiovascular compromise. Most fetuses with abnormal cardiac output or right ventricular dysfunction normalized post-therapy. There was no relationship between cardiac output and obstetric markers. CONCLUSIONS: Elevated indexed cardiac output is strongly associated with cardiovascular compromise. Traditional obstetric prognosticators do not correlate with cardiovascular derangements. In pump twins with cardiac compromise, postoperative cardiovascular status improves acutely. Given this analysis, we conclude that assessment of cardiovascular findings should be incorporated into the management and treatment of TRAP sequence.

An embolic complication in a donor twin with severe twin-twin transfusion syndrome after fetoscopic intervention.

Necrotic injury of an extremity in a donor twin is a rare complication of twin-twin transfusion syndrome after selective fetoscopic laser photocoagulation. We present the case of a 20-year-old gravida 2, para 1 with a twin gestation with severe twin-twin transfusion syndrome (Quintero Stage 3B) who had treatment with selective fetoscopic laser photocoagulation. Selective fetoscopic laser photocoagulation may be associated with extremity necrosis in a donor twin.

Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin transfusion syndrome: relation to Quintero stage.

OBJECTIVES: To examine cardiac structural and functional changes in twin-twin transfusion syndrome (TTTS), relative to Quintero stage, as a means of evaluating the spectrum of cardiomyopathy in TTTS. METHODS: This was a cross-sectional, retrospective study of 42 consecutive cases of TTTS referred to a single fetal therapy center. Quintero stages were assigned by standard criteria. Presence of ventricular hypertrophy, cardiomegaly, atrioventricular valve regurgitation (AVVR), ventricular systolic dysfunction and right ventricular outflow tract obstruction on fetal echocardiography were noted. The Doppler myocardial performance index (MPI), an index of global ventricular function, was calculated for both ventricles in subjects with adequate Doppler data. We compared cardiac changes across Quintero stages. RESULTS: There was no cardiomyopathy observed in donor twins. The majority of subjects presented at Quintero Stage I (n = 14), II (n = 14) or III (n = 11), with fewer at Stages IV (n = 2) or V (n = 1). As early as Quintero Stages I and II, a significant proportion of recipient twins had ventricular hypertrophy (17/28, 61%), AVVR (6/28, 21%) or quantitative abnormalities in either right (12/24, 50%) or left (14/24, 58%) ventricular function. Increasing prevalence of biventricular systolic dysfunction and cardiomegaly accompanied advancing Quintero stage. CONCLUSIONS: Changes in cardiac structure and function not reflected in Quintero staging occur in recipient twins early in the evolution of TTTS. Incorporation of cardiac findings into assessment of TTTS severity may prove useful in stratification of risk and treatment selection.

Alpha5 and alpha2 integrin gene transfers mimic the PDGF-B-induced transformed phenotype of fibroblasts in human skin.

Platelet-derived growth factor (PDGF)-B is a proto-oncogene capable of transforming fibroblasts. Using adenoviral vectors, we tested whether endogenous PDGF-B expression in human skin xenotransplants leads to changes in the expression of alpha5 and alpha2 integrin subunits and whether integrin overexpression leads to PDGF-related changes in the skin. In vitro, transduction of fibroblasts with PDGF-B or the integrin alpha5 subunit stimulated multilayered growth and spindle-type morphology, both markers of mesenchymal cell transformation. In vivo, PDGF-B transduction of the human dermis was associated with up-regulation of collagen and fibronectin synthesis, increases in alpha5 and alpha2 integrin subunit expression, vessel formation, and proliferation of fibroblasts, keratinocytes, and pericytes. A similar stromal response was induced when alpha5 and alpha2 integrin subunits were overexpressed in the human dermis, suggesting that integrins play a major role in the induction of a transformed phenotype of fibroblasts by PDGF-B.

Synthetic hybrid grafts for craniofacial reconstruction: sustained gene delivery using a calcium phosphate bone mineral substitute.

These experiments were performed to evaluate the efficacy of a biocompatible bone cement, Norian CRS, engineered as a hybrid graft for simultaneous bone matrix reconstruction and sustained, site-directed gene transfer using an adenoviral vector. Norian CRS was cured ex vivo by mixing a calcium source powder with a phosphate source solution to form a paste. To 1.0 ml of the cement was added 50 microl of a solution containing 1 x 10(8) plaque-forming units of a replication-deficient adenoviral vector containing a bacterial beta-galactosidase reporter gene (AdLacZ). In vitro, fragments of the hybrid Norian-AdLacZ construct were placed into 12-microm-pore culture plate inserts and cocultured with human fibroblasts. The same insert was transferred to a new well of fibroblasts every 48 hours for 30 days, and, after allowing 72 hours for gene expression, fibroblasts were examined for transgene expression by 5 bromo-4-chloro-3-indoyl-beta-D-galactosidase (X-gal) staining. In vivo, the Norian-AdLacZ hybrid was implanted into 10-mm frontal bone defects in 3-week-old piglets. The implant sites were harvested after 5 days and were examined for transgene expression by X-gal staining. X-gal staining of fibroblasts incubated with the hybrid Norian-AdLacZ construct was observed throughout the 30-day period. Transgene expression was also observed about the periphery of the calvarial defects treated with hybrid Norian-AdLacZ constructs. Thus, adenoviral vectors may be incorporated successfully into a synthetic calcium phosphate bone mineral substitute to provide effective, sustained local gene delivery.

Matrix immobilization enhances the tissue repair activity of growth factor gene therapy vectors.

Although growth factor proteins display potent tissue repair activities, difficulty in sustaining localized therapeutic concentrations limits their therapeutic activity. We reasoned that enhanced histogenesis might be achieved by combining growth factor genes with biocompatible matrices capable of immobilizing vectors at delivery sites. When delivered to subcutaneously implanted sponges, a platelet-derived growth factor B-encoding adenovirus (AdPDGF-B) formulated in a collagen matrix enhanced granulation tissue deposition 3- to 4-fold (p < or = 0.0002), whereas vectors encoding fibroblast growth factor 2 or vascular endothelial growth factor promoted primarily angiogenic responses. By day 8 posttreatment of ischemic excisional wounds, collagen-formulated AdPDGF-B enhanced granulation tissue and epithelial areas up to 13- and 6-fold (p < 0.009), respectively, and wound closure up to 2-fold (p < 0.05). At longer times, complete healing without excessive scar formation was achieved. Collagen matrices were shown to retain both vector and transgene products within delivery sites, enabling the transduction and stimulation of infiltrating repair cells. Quantitative PCR and RT-PCR demonstrated both vector DNA and transgene mRNA within wound beds as late as 28 days posttreatment. By contrast, aqueous formulations allowed vector seepage from application sites, leading to PDGF-induced hyperplasia in surrounding tissues but not wound beds. Finally, repeated applications of PDGF-BB protein were required for neotissue induction approaching equivalence to a single application of collagen-immobilized AdPDGF-B, confirming the utility of this gene transfer approach. Overall, these studies demonstrate that immobilizing matrices enable the controlled delivery and activity of tissue promoting genes for the effective regeneration of injured tissues.

Treatment of severe congenital diaphragmatic hernia by fetal tracheal occlusion: clinical experience with fifteen cases.

OBJECTIVE: Our purpose was to determine whether prenatal tracheal occlusion improves survival in a selected population of fetuses affected by severe congenital diaphragmatic hernia. STUDY DESIGN: Fetuses with isolated congenital diaphragmatic hernia were selected as candidates for fetal intervention by specific criteria designed to predict a 90% mortality rate with conventional postnatal treatment. RESULTS: Fifteen fetuses underwent tracheal occlusion with 5 survivors (33%). Two fetuses were lost to early preterm labor. In 13 mothers, postoperative gestation ranged from 19 to 68 days, with a mean duration of pregnancy after tracheal occlusion of 38 days. The 5 survivors were hospitalized for an average of 76 days. Despite dramatic lung growth in some fetuses after tracheal occlusion, intensive management was required, and most deaths were caused by respiratory insufficiency. CONCLUSION: Prenatal tracheal occlusion can result in impressive lung growth in a subset of fetuses with severe congenital diaphragmatic hernia. However, survival remains compromised by pulmonary functional abnormality and the consequences of prematurity.

Assessment of fetal lung volumes and liver herniation with magnetic resonance imaging in congenital diaphragmatic hernia.

OBJECTIVE: We evaluated the use of fetal magnetic resonance imaging in predicting outcomes after ultrasonographic diagnosis of left-sided congenital diaphragmatic hernia. STUDY DESIGN: Forty-one pregnant women carrying fetuses with congenital diaphragmatic hernia underwent 43 magnetic resonance imaging scans. Lung volumes were calculated by summing the areas on 6-mm axial sections. The presence or absence of liver herniation was noted. A liver/diaphragm ratio was obtained by using the distances from the superior aspect of the liver and the diaphragmatic remnant to the apex of the chest. RESULTS: Mean gestational age was 26 weeks and overall survival was 59%. Neither right, left, nor total lung volume measurements were predictive of survival. Liver herniation into the left side of the chest was predictive of outcome at P<.05. The liver/diaphragm ratio was predictive of outcome at P = .03. CONCLUSION: Fetal magnetic resonance imaging permits calculation of lung volumes, but these volumes are not predictive of outcome. However, both the presence of liver herniation and the volume of liver within the chest, as reflected by the liver/diaphragm ratio, help predict outcome in left-sided congenital diaphragmatic hernia.

Anesthesia for fetoscopic fetal surgery: twin reverse arterial perfusion sequence and twin-twin transfusions syndrome.

IMPLICATIONS: Twin reversed arterial perfusion sequence and twin-twin transfusion syndrome can be managed by fetoscopic fetal surgery. It is important to consider the fetal, uteroplacental, and maternal issues when choosing an anesthetic technique. We report on three patients with differing anesthetic issues using fetoscopic surgery for umbilical cord coagulation.

Salvage of a fetus with congenital high airway obstruction syndrome by ex utero intrapartum treatment (EXIT) procedure.

A fetus with congenital high airway obstruction syndrome (CHAOS) due to complete tracheal atresia was referred at 31 weeks of gestation after 12 weeks of massive hydrops. The fetus was delivered by the ex utero intrapartum treatment procedure allowing sufficient time while on placental support for bronchoscopy to confirm tracheal atresia and tracheostomy to secure the airway. His postnatal course was complicated by severe capillary leak syndrome secondary to hydrops, diaphragmatic paralysis, tracheobronchial malacia, and the need for chronic ventilatory support. The infant's tracheobronchial malacia resolved by 5 months of age and normal diaphragmatic function was restored at 9 months allowing him to be weaned from mechanical ventilation. He underwent tracheal reconstruction at 17 months of age. At follow up at 32 months of age he has a patent airway and is the first long-term survivor with CHAOS.