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Alan W Flake

Publications and source records attributed to Alan W Flake.

At least 55 records · Page 3Linked to original sources
PubMed2003

Fetal heart development in the nitrofen-induced CDH rat model: the role of mechanical and nonmechanical factors.

BACKGROUND/PURPOSE: In congenital diaphragmatic hernia (CDH), it was recently shown that early and late gestational lung underdevelopment is caused by nonmechanical and mechanical factors, respectively. Heart underdevelopment, which might predict lung hypoplasia, is commonly attributed to mechanical factors. The authors analyzed whether nonmechanical and mechanical factors affect cardiac growth and correlations between lung and heart weights during gestation. METHODS: Left-sided CDH was induced in pregnant Wistar rats by administration of nitrofen on E9.5. At selected gestational ages (E18, E20, and E22), the lungs and heart were harvested, weighed, and analyzed for DNA and protein contents. Left lung and heart weights were correlated at those gestational ages. Two experimental groups: nitrofen without CDH (nitrofen), and nitrofen with CDH (CDH), were compared with normal controls. RESULTS: At E18, both nitrofen-exposed groups presented similar and significant left lung (LL) hypoplasia. As gestation progressed (E20 and E22), in the nitrofen group left lung (LL) hypoplasia decreased, whereas in the CDH group LL hypoplasia was exacerbated relative to normal controls. In contrast, at E18 and E20, heart-to-body weight ratios as well as cardiac DNA and protein contents were reduced significantly in all animals exposed to nitrofen, with no significant differences observed between nitrofen and CDH groups. As gestation progressed, the difference between cardiac parameters in nitrofen-exposed and normal control rats diminished, and at E22 no significant differences were documented. In the CDH group, significant correlations were seen between lung and heart weights at E18 (r = 0.65; P <.05) and E20 (r = 0.4; P <.05), whereas at term gestation (E22) no significant correlation was observed (r = 0.21, not significant). CONCLUSIONS: Nonmechanical factors, which might be directed by nitrofen, play a role in the pathogenesis of lung and heart hypoplasia manifested precociously in fetal life, whereas mechanical compression might influence only lung growth during late gestation. Heart weight predicts lung weight only in early gestational ages.

Animals↗
PubMed2003

Mixed chimerism following in utero hematopoietic stem cell transplantation in murine models of hemoglobinopathy.

OBJECTIVE: Mixed hematopoietic chimerism after bone marrow transplantation can provide effective treatment for beta-thalassemia because of the selective advantage that exists for donor erythropoiesis. In utero hematopoietic stem cell transplantation (IUHSCTx) can achieve mixed hematopoietic chimerism, particularly when a selective advantage exists for donor cells. To investigate the biology of IUHSCTx in hemoglobinopathies, we performed fully allogeneic IUHSCTx in murine models of beta-thalassemia (Thal) and sickle cell disease (SCD). MATERIALS AND METHODS: We serially assessed and compared levels of mononuclear cell (MNC) and erythroid chimerism after IUHSCTx of either adult bone marrow (BM)- or fetal liver (FL)-derived allogeneic donor cells in the two hemoglobinopathy models, which differ significantly in their degree of anemia (Thal>>SCD) and red cell half-life (Thal<<SCD). RESULTS: The mean level of donor MNC chimerism was higher for SCD and Thal chimeras receiving FL- compared to adult BM-derived donor cells and tended to increase over time in the FL recipients. Donor hemoglobin (Hb) levels also were higher in all groups receiving FL compared to adult BM. Donor Hb levels in chimeric Thal mice were significantly higher than those in SCD or wild-type mice. Hematologic parameters such as Hb, hematocrit (Hct), mean cell volume (MCV), membrane-associated denatured Hb, and the oxygen equilibration curve were improved in chimeric hemoglobinopathy mice. However, the improvement in Hb, Hct, and MCV was not sustained despite stable levels of donor leukocyte engraftment. CONCLUSION: The severity of the hemoglobinopathy being treated and the source of donor cells may be important determinants of success in the treatment of hemoglobinopathy by IUHSCTx.

Anemia, Sickle Cell↗
PubMed2003

Stem cell and genetic therapies for the fetus.

In the near future, prenatal therapy may include stem cell-based cellular therapy or gene therapy. There is considerable overlap in the rationale and potential applications for these 2 approaches. The purpose of this manuscript is to consider current progress in both areas relevant to prenatal treatment. Although clinical application is currently limited to a few highly selected disorders that are amenable to cellular therapy, there is reason to believe that a dramatic increase in application will occur in the near future.

Female↗
PubMed2003

Management of congenital lung lesions.

The prenatal diagnostic hallmarks, natural history, and management of congenital cystic adenomatoid malformation of the lung and pulmonary sequestration are reviewed. Large lung tumors may disappear partially on serial prenatal sonography, suggesting that improvement can occur occasionally during fetal life. The fetus with a lung mass but without hydrops has an excellent chance for survival with maternal transport, planned delivery, and postnatal evaluation and surgery. The finding that fetuses with hydrops are at very high risk for fetal or neonatal death has led to successful fetal thoracoamniotic shunt placement or fetal surgical resection.

Bronchopulmonary Sequestration↗
PubMed2003

Fetal myelomeningocele repair: short-term clinical outcomes.

OBJECTIVE: The study was undertaken to evaluate short-term clinical outcomes with antenatal myelomeningocele (MMC) repair. STUDY DESIGN: Retrospective review of 50 fetuses that underwent open fetal MMC closure was performed. Inclusion criteria included less than 26 weeks' gestation, thoracic to S1 level defect, absent clubfoot deformity, Arnold-Chiari malformation, ventriculomegaly less than 17 mm, normal karyotype, and no other anomalies. RESULTS: Perinatal survival was 94% (47/50 fetuses). Mean age at delivery was 34 weeks 3 days. All fetuses demonstrated reversal of hindbrain herniation. Forty-three percent of the 50 fetuses have required ventriculoperitoneal shunting compared with 100% thoracic, 88% lumbar, and 68% sacral (85% overall) in 297 historic controls. Better-than-predicted leg function was seen in 57% of thoracic and lumbar level lesion patients. CONCLUSION: Early experience with fetal MMC repair suggests a decreased need for ventriculoperitoneal shunting, arrest or slowing of progressive ventriculomegaly, and consistent resolution of hindbrain herniation. However, further long-term follow-up is needed to evaluate neurodevelopment and bladder and bowel function.

Adult↗
PubMed2003

Temporary tracheal occlusion in fetal sheep with lung hypoplasia does not improve postnatal lung function.

Prolonged fetal tracheal occlusion (TO) accelerates lung growth but leads to loss of alveolar epithelial type II (AE2) cells. In contrast, temporary TO leads to recovery of AE2 cells and their ability to produce surfactant. The aim of this study was to determine the effects of temporary TO in fetal sheep with lung hypoplasia on postnatal lung function, structure, and surfactant protein mRNA expression. Diaphragmatic hernia (DH) was created in 22 fetal sheep at 65 days of gestation. TO was performed between 110 days of gestation and full term (DH/TO, n = 7) and between 110 and 130 days of gestation (DH/TO+R, n = 6). Sham-operated fetuses (n = 11) served as controls. Lambs were delivered at approximately 139 days of gestation, and blood gas tensions were monitored over a 2-h resuscitation period. Temporary TO increased growth of the hypoplastic lung and restored surfactant protein mRNA expression and AE2 cell density but did not improve respiratory function above that of animals that underwent prolonged TO; DH/TO and DH/TO+R lambs were hypoxic and hypercapnic compared with Sham animals. Lung compliance remained low in DH/TO+R lambs, most likely as a consequence of the persistent increase in alveolar wall thickness in these animals.

Animals↗
PubMed2002

AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B.

Hemophilia B is an X-linked coagulopathy caused by absence of functional coagulation factor IX (F.IX). Previously, we established an experimental basis for gene transfer as a method of treating the disease in mice and hemophilic dogs through intramuscular injection of a recombinant adeno-associated viral (rAAV) vector expressing F.IX. In this study we investigated the safety of this approach in patients with hemophilia B. In an open-label dose-escalation study, adult men with severe hemophilia B (F.IX < 1%) due to a missense mutation were injected at multiple intramuscular sites with an rAAV vector. At doses ranging from 2 x 10(11) vector genomes (vg)/kg to 1.8 x 10(12) vg/kg, there was no evidence of local or systemic toxicity up to 40 months after injection. Muscle biopsies of injection sites performed 2 to 10 months after vector administration confirmed gene transfer as evidenced by Southern blot and transgene expression as evidenced by immunohistochemical staining. Pre-existing high-titer antibodies to AAV did not prevent gene transfer or expression. Despite strong evidence for gene transfer and expression, circulating levels of F.IX were in all cases less than 2% and most were less than 1%. Although more extensive transduction of muscle fibers will be required to develop a therapy that reliably raises circulating levels to more than 1% in all subjects, these results of the first parenteral administration of rAAV demonstrate that administration of AAV vector by the intramuscular route is safe at the doses tested and effects gene transfer and expression in humans in a manner similar to that seen in animals.

Adult↗
PubMed2002

High-level allogeneic chimerism achieved by prenatal tolerance induction and postnatal nonmyeloablative bone marrow transplantation.

Clinical application of allogeneic bone marrow transplantation (BMT) has been limited by toxicity related to cytoreductive conditioning and immune response. In utero hematopoietic stem cell transplantation (IUHSCT) is a nonablative approach that achieves mixed chimerism and donor-specific tolerance but has been limited by minimal engraftment. We hypothesized that mixed chimerism achieved by IUHSCT could be enhanced after birth by nonmyeloablative total body irradiation (TBI) followed by same-donor BMT. To test this hypothesis, mixed chimerism was created by IUHSCT in a major histocompatibility complex-mismatched strain combination. After birth, chimeric animals received nonmyeloablative TBI followed by transplantation of donor congenic bone marrow cells. Our results show that: (1) low-level chimerism after IUHSCT can be enhanced to high-level chimerism by this strategy; (2) enhancement of chimerism is dependent on dose of TBI; (3) the mechanism of TBI enhancement is via a transient competitive advantage for nonirradiated hematopoietic stem cells; (4) engraftment observed in the tolerant, fully allogeneic IUHSC transplant recipient is equivalent to a congenic recipient; and (5) host-reactive donor lymphocytes are deleted with no evidence of graft-versus-host disease. This study supports the concept of prenatal tolerance induction to facilitate nonmyeloablative postnatal strategies for cellular therapy. If clinically applicable, such an approach could dramatically expand the application of IUHSCT.

Animals↗
PubMed2002

Surgery in the human fetus: the future.

Fetal surgery was born of clinical necessity. Observations by pediatric surgeons and neonatologists of neonates that were born with irreversible organ damage led to the conclusion that one possible approach to prevent this alteration of developmental physiology, was fetal surgical intervention. This led to experimental validation of the pathophysiology of specific fetal defects in animal models and to the development of techniques for their prenatal surgical correction. The demonstration in animal models that the correction of an anatomical defect could reverse the associated pathophysiology led to the first systematic application of fetal surgery at the University of California, San Francisco, in the early 1980s. Since that time, fetal surgery has been applied in only a few centres and has remained relatively limited in scope. Nevertheless, there has been a dramatic improvement in our ability to diagnose, select and safely operate on an expanding number of fetal anomalies. The purpose of this article is to briefly summarize the present status of fetal surgery and to speculate about what may be in store for the future. Inherent in such an effort is a definition of what constitutes fetal surgery. In this discussion I will take considerable latitude with the definition of what constitutes fetal surgery in the future, as it is my belief that technological progress in a number of areas will result in dramatic changes in the practice and perception of fetal surgery.

Female↗
PubMed2002

Complete allogeneic hematopoietic chimerism achieved by a combined strategy of in utero hematopoietic stem cell transplantation and postnatal donor lymphocyte infusion.

In utero hematopoietic stem cell transplantation (IUHSCTx) can achieve mixed hematopoietic chimerism and donor-specific tolerance without cytoreductive conditioning or immunosuppression. The primary limitation to the clinical application of IUHSCTx has been minimal donor cell engraftment, well below therapeutic levels for most target diseases. Donor lymphocyte infusion (DLI) has been used in postnatal circumstances of mixed chimerism as targeted immunotherapy to achieve a graft-versus-hematopoietic effect and to increase levels of donor cell engraftment. In this report we demonstrate in the murine model that a combined approach of IUHSCTx followed by postnatal DLI can convert low-level, mixed hematopoietic chimerism to complete donor chimerism across full major histocompatibility complex barriers with minimal risk for graft-versus-host disease (GVHD). Time-dated embryonic day 14 (E14) to E15 Balb/c (H-2K(d), CD45.2) fetuses underwent intraperitoneal injection of 5 x 10(6) T-cell-depleted B6 (H-2K(b), CD45.2) bone marrow cells. Chimeric recipients then received transplants at either 4 or 8 weeks of age with 1 of 3 doses (5, 15, or 30 x 10(6) cells) of donor congenic splenocytes (B6-Ly5.2/Cr, H-2K(b), CD45.1). The response to DLI was dose dependent, with conversion to complete donor peripheral blood chimerism in 100% of animals that received high-dose (30 x 10(6) cells) DLI. Only 1 of 56 animals receiving this dose succumbed to GVHD. This study directly supports the potential therapeutic strategy of prenatal tolerance induction to facilitate nontoxic postnatal cellular therapy and organ transplantation, and it has broad implications for the potential treatment of prenatally diagnosed genetic disorders.

Animals↗
PubMed2002

Efficient transduction of liver and muscle after in utero injection of lentiviral vectors with different pseudotypes.

In this study we investigate the efficacy of lentiviral vectors of different pseudotypes for gene transfer to tissues of the preimmune fetus. BALB/c fetuses at 14-15 days' gestation received lentiviral vectors carrying the transgene lacZ under the control of the human cytomegalovirus (CMV) promoter by intramuscular (i.m.) or intrahepatic (i.h.) injection. We pseudotyped the lentiviral vectors with vesicular stomatitis virus (VSV-G), with Mokola virus, or with Ebola virus envelope glycoproteins. We harvested the pups at time points between 5 days and 9 months following injection and performed a detailed histologic assessment. The efficiency and distribution of transduction after in utero administration was highly dependent upon the route of administration and the pseudotype of vector used. Biodistribution studies showed widespread distribution of vector sequences in multiple tissues, albeit at very low levels, and transduced cells were found in significant numbers only in liver, heart, and muscle. Overall, VSV-G was the most efficient in transducing hepatocytes, whereas Mokola and Ebola were more efficient in transducing myocytes. Transduction of cardiomyocytes was observed after both i.m. and i.h. injection of all three vectors. Our findings of long-term transduction of skeletal myocytes and cardiomyocytes after in utero administration suggest a novel strategy for the treatment of congenital muscular dystrophies.

Animals↗
PubMed2002

A novel small animal model of left ventricular tissue engineering.

BACKGROUND: Complex congenital cardiac anomalies involving ventricular hypoplasia require either staged palliative reconstruction, converting the circulatory system to a single ventricle based pump, or allogeneic transplantation. Tissue engineering offers the potential for complete reconstruction of these defects, but is limited by the inability to model myocardial tissue engineering in a small animal. Our goal was to develop a small animal model for ventricular tissue engineering using rat heterotopic heart transplantation. METHODS: Donor hearts were explanted after cardioplegic arrest and the left ventricular volume was augmented by the implantation of a biodegradable engineered construct. The heart was then transplanted heterotopically into syngeneic recipients creating either a volume loaded, functioning left ventricle, or a non-functioning left ventricle. Some of the engineered constructs were seeded with multipotent bone marrow-derived mesenchymal progenitor cells before implantation. Animals were evaluated by echocardiography, morphology, histology, and immunohistochemistry after 1 month. RESULTS: A scaffolding constructed from polytetrafluoroethylene, polylactide mesh, and type I and IV collagen hydrogel resulted in minimal intracardiac inflammation without aneurysmal dilatation. Successful transplantation and differentiation of mesenchymal progenitor cells was accomplished using this scaffolding. No ventricular arrhythmias resulted from this surgical manipulation and echocardiography revealed both end systolic and diastolic volume augmentation with ventricular expansion. CONCLUSION: We have developed an in vivo model of ventricular tissue engineering using heterotopic heart transplantation. Future work will focus on construction of ventricular tissue around pre-fabricated vascular networks in order increase cellular engraftment for ventricular reconstruction.

Animals↗
PubMed2002

Fetal therapy.

Over the past 40 years, a small but increasing number of fetal genetic and congenital anomalies has become amenable to in utero treatment. Successful fetal therapies have included open procedures for congenital diaphragmatic hernia, cystadenomatoid malformation of the lung and saccrococygeal teratoma, shunts for uropathies and thoracic fluids, pharmacological therapies for congenital adrenal hyperplasia and neural tube defect prevention, and the stem cell treatment of severe combined immunodeficiency disorder.

Adrenal Hyperplasia, Congenital↗
PubMed2002

Meconium dependence of bowel damage in gastroschisis.

BACKGROUND/PURPOSE: Increasing evidence of physiologic in utero defecation supports the hypothesis that bowel damage in gastroschisis may be meconium dependent. In this study, the author investigated the role of meconium on parameters of bowel damage in a fetal rat model of gastroschisis. METHODS: Pregnant rats underwent laparotomy at 18 1/2 days gestational age (GA). There were 4 experimental groups of 11 fetuses each; the G(M) group consisted of fetuses with isolated gastroschisis and was considered to have moderate meconium contamination of the amniotic fluid (MCAF); the G(L) group consisted of fetuses with gastroschisis and anal ligation, performed to prevent MCAF; the G(H) group consisted of fetuses with gastroschisis and colon perforation, performed to increase MCAF; and the Sham group consisted of sham operated controls. All fetuses were harvested by cesarean section at 21 1/2 days GA, and the fetal intestine was assessed for peel, intestinal length, intestinal weight per unit length, and histologic appearance. RESULTS: The authors achieved the following fetal survival rates: G(M) group, 91% (10 of 11); G(L) group, 78% (7 of 9, the ligation was not successful in 2 fetuses); G(H) group, 82% (9 of 11). Sham group, 100% (11 of 11). Intestinal length was decreased in fetuses with gastroschisis, and this reduction was related directly to the grade of MCAF (Sham, 18.4 +/- 0.6; G(L), 11.5 +/- 0.5; G(M), 10.2 +/- 0.6; G(H), 9.1 +/- 0.6 cm; P <.01). In contrast, intestinal weight per unit length increased in fetuses with gastroschisis, and this increase was related directly to the grade of MCAF (Sham, 7.8 +/- 0.5; G(L), 9.4 +/- 0.5; G(M), 11.3 +/- 0.5; G(H), 16.9 +/- 0.7 mg/cm; P <.01). In comparison with the G(M) group, the degree of peel coverage and bowel adherence were increased markedly in the G(H) group, whereas the fetuses of the G(L) group had neither peel nor bowel adherence. CONCLUSIONS: All bowel damage parameters were affected by MCAF supporting the hypothesis that bowel damage in gastroschisis is at least partially dependent on meconium exposure. Further research is required to clarify other factors that contribute to bowel damage and to identify risk factors that may allow prenatal identification of severely affected fetuses.

Amniotic Fluid↗
PubMed2002

The natural history of prenatally diagnosed conjoined twins.

BACKGROUND/PURPOSE: Accurate prenatal diagnosis of complex anatomic connections and associated anomalies has only been possible recently with the use of ultrasonography, echocardiography, and fetal magnetic resonance imaging (MRI). To assess the impact of improved antenatal diagnosis in the management and outcome of conjoined twins, the authors reviewed their experience with 14 cases. METHODS: A retrospective review of prenatally diagnosed conjoined twins referred to our institution from 1996 to present was conducted. RESULTS: In 14 sets of conjoined twins, there were 10 thoracoomphalopagus, 2 dicephalus tribrachius dipus, 1 ischiopagus, and 1 ischioomphalopagus. The earliest age at diagnosis was 9 weeks' gestation (range, 9 to 29; mean, 20). Prenatal imaging with ultrasonography, echocardiography, and ultrafast fetal MRI accurately defined the shared anatomy in all cases. Associated anomalies included cardiac malformations (11 of 14), congenital diaphragmatic hernia (4 of 14), abdominal wall defects (2 of 14), and imperforate anus (2 of 14). Three sets of twins underwent therapeutic abortion, 1 set of twins died in utero, and 10 were delivered via cesarean section at a mean gestational age of 34 weeks. There were 5 individual survivors in the series after separation (18%). In one case, in which a twin with a normal heart perfused the cotwin with a rudimentary heart, the ex utero intrapartum treatment procedure (EXIT) was utilized because of concern that the normal twin would suffer immediate cardiac decompensation at birth. This EXIT-to-separation strategy allowed prompt control of the airway and circulation before clamping the umbilical cord and optimized control over a potentially emergent situation, leading to survival of the normal cotwin. In 2 sets of twins in which each twin had a normal heart, tissue expanders were inserted before separation. CONCLUSIONS: Advances in prenatal diagnosis allow detailed, accurate evaluations of conjoined twins. Careful prenatal studies may uncover cases in which emergent separation at birth is lifesaving.

Female↗
PubMed2002

Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung.

BACKGROUND/PURPOSE: Cystic adenomatoid malformation of the lung (CAM) diagnosed in utero has a variable natural history that may result in hydrops in up to 40% or regress in up to 15%. No criteria have been available to determine which lesions would grow and develop hydrops versus those whose growth would stabilize or regress. To better understand the natural history of CAM the authors developed a measure of tumor volume normalized for gestation age, the CAM volume ratio, or CVR. The results of an initial retrospective review of CVR at presentation suggested its usefulness as a predictor of outcome in CAM. The authors now report the results of prospective use of the CVR both to track tumor growth and regression during gestation and confirm its predictive value in fetuses with CAM. METHODS: In the retrospective review performed between November 1998 and August 1999, 32 fetuses with CAM were reviewed and divided into those with hydrops and those in whom hydrops never developed. The CVR was determined by measuring 3 dimensions of the CAM using the formula for the volume of an ellipse and dividing by the head circumference to correct for differences in gestational age. Of the 32 fetuses in the retrospective study, the 8 that had hydrops had a significantly higher CVR (3.1 plus minus 1.1) compared with hydropic fetuses (0.74 plus minus 0.48; P <.001). The mean of the nonhydropic fetus's CVR plus 2 standard deviations (0.74 + 0.96 = 1.7) was used as a cutoff in the subsequent prospective study. From September 1, 1999 through March 1, 2001, the authors evaluated prospectively 58 patients with CAM by CVR measurement. These patients were followed up with serial ultrasound scans, and CVR at presentation correlated with the development of hydrops, survival, need for fetal intervention, and the need for ventilatory support or extracorporeal membrane oxygenation (ECMO), and length of hospital stay postnatally. The indication for fetal intervention was the development of hydops. RESULTS: The fetuses with CVR less-than-or-equal1.6 (n = 42) were considered to be at low risk for the development of hydrops, and those with CVR greater than 1.6 (n = 16) were considered at increased risk for developing hydrops. Of the 42 fetuses in the low-risk group, 7 (16.7%) developed hydrops, and all but 1 had a dominant cyst. If CAMs with a dominant cyst are excluded, only 1 of 36 (2.8%) of CAMs with CVR less-than-or-equal 1.6 developed hydrops (P <.001). In fetuses with CVR at presentation more than 1.6, 12 of 16 (75%; P <.005) developed hydrops. Seventeen fetuses underwent fetal treatment (8 CVR less-than-or-equal 1.6; 9 CVR > 1.6): 7 patients required open fetal surgery (survival rate, 2 of 7), 6 patients thoracoamniotic shunting (survival rate, 6 of 6); and 4 patients cyst aspiration (survival rate, 4 of 4). All survivors of fetal intervention required at a least brief period of ventilatory support; none required ECMO. CONCLUSIONS: A CVR of greater than 1.6 at presentation accurately predicts increased risk of hydrops developing in CAM. A CVR of less-than-or-equal1.6 at presentation suggests that the risk of hydrops developing in the absence of a dominant cyst is less than 3%. The CVR is a useful sonographic indicator of fetuses at risk for hydrops who require close ultrasound observation and possible fetal intervention.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed2002

The EXIT procedure: experience and outcome in 31 cases.

BACKGROUND: The EXIT (ex utero intrapartum treatment) procedure, although initially designed for reversal of tracheal occlusion in fetuses with congenital diaphragmatic hernias (CDH), has been adapted to treat a variety of fetal conditions. METHODS: A retrospective chart review of all consecutive EXIT procedures since 1996 was conducted. RESULTS: Thirty-one women underwent the EXIT procedure, with an average maternal age of 29 years (range, 20 to 38), and average gestational age of 34 weeks (range, 29 to 40). The indication was airway obstruction from fetal neck mass in 13, and reversal of tracheal occlusion from in utero clipping in 13. Singular indications included an EXIT-to-ECMO (extracorporeal membrane oxygenation) procedure for a fetus with CDH and a cardiac defect (n = 1), congenital high airway obstruction syndrome (CHAOS, n = 1), resection of a very large congenital cystic adenomatoid malformation of the lung (CCAM) on uteroplacental bypass (n = 1), unilateral pulmonary agenesis (n = 1), and thoracoomphalopagus conjoined twins. The mean duration on uteroplacental bypass (from uterine incision to umbilical cord clamping) was 30.3 plus minus 14.7 minutes (range, 8 to 66). No fetus experienced hemodynamic instability during uteroplacental bypass as recorded by fetal heart rate (FHR), pulse oximeter, and fetal echocardiography, except for one instance of reversible bradycardia from umbilical cord compression. The mean FHR and fetal saturation were 153.0 plus minus 38.5 beats per minute and 71.2% plus minus 19.9%, respectively. Five fetuses required a tracheostomy. Only 1 death occurred during an EXIT procedure because of inability to secure the airway secondary to extensive involvement by a lymphangioma. The average cord pH and pCO(2) were, respectively, 7.20 plus minus 0.11 and 63.2 plus minus 14.6. Two maternal complications occurred: bleeding from a hysterotomy site and dehiscence of an old hysterotomy scar noticed at a subsequent cesarean section. The average maternal blood loss was 848.3 plus minus 574.1 mL. CONCLUSION: The EXIT procedure was used successfully to ensure uteroplacental gas exchange and fetal hemodynamic stability during a variety of surgical procedures performed to secure the fetal airway or ensure successful transition to postnatal environment.

Adult↗