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Alan W Flake

Publications and source records attributed to Alan W Flake.

At least 37 records · Page 2Linked to original sources
PubMed2005

Antenatal vitamin A administration attenuates lung hypoplasia by interfering with early instead of late determinants of lung underdevelopment in congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Early and late lung underdevelopment in congenital diaphragmatic hernia (CDH) is likely caused by nonmechanical (directly mediated by nitrofen) and mechanical (mediated by thoracic herniation) factors, respectively. The authors investigated if vitamin A enhances lung growth because of effects on both early and late determinants of lung hypoplasia. METHODS: Twenty-seven pregnant Wistar rats were exposed on embryonic day (E)9.5 to 100 mg of nitrofen or just olive oil. From nitrofen-exposed pregnant rats, 12 were treated at day 9.5 or 18.5 with 15,000 IU of vitamin A. Lungs were harvested at E18, E20, and E22, weighed, and analyzed for DNA and protein contents. Left and/or right lung hypoplasia was estimated by assessment of the ratios of lung to body weight and left to right lung weight. Fetuses were assigned to 5 experimental groups: baseline (exposed neither to nitrofen nor vitamin A), nitrofen (exposed to nitrofen without CDH), CDH (exposed to nitrofen with CDH), nitr+vitA (exposed to nitrofen without CDH and treated with vitamin A), and CDH+vitA (exposed to nitrofen with CDH and treated with vitamin A). RESULTS: Incidence of hernia was significantly reduced in fetuses treated with vitamin A. When vitamin A was administered at E9.5, the authors observed similar effect on lung hypoplasia measured through ratio of lung to body weight at E18 in the nitrofen and CDH groups (nitrofen 1.92% +/- 0.05%, CDH 1.92% +/- 0.04%), whereas lung hypoplasia was attenuated relative to baseline (2.45% +/- 0.05%) in 5% and 4% in nitrofen (nitr+vitA 2.05% +/- 0.03%) and CDH (CDH+vitA 2.08% +/- 0.04%) groups, respectively. At E20, lung hypoplasia was increased in CDH compared with nitrofen groups (nitrofen 2.52% +/- 0.1%, CDH 2.39% +/- 0.05%), whereas vitamin A attenuated lung hypoplasia, in relation to baseline (3.20% +/- 0.07%), 14% in both nitrofen-exposed groups (nitr+vitA 2.96% +/- 0.03%, CDH+vitA 2.83% +/- 0.03%). At E22, lung hypoplasia was significantly higher in CDH group than nitrofen group (nitrofen 2.13% +/- 0.06%, CDH 1.48% +/- 0.03%), whereas lung hypoplasia was attenuated in 9% of both nitrofen-exposed groups (nitr+vitA 2.35% +/- 0.06%, CDH+vitA 1.69% +/- 0.05%) in relation to baseline group (2.38% +/- 0.04%). Administration of vitamin A at E18.5 produced no significant effects on lung growth. CONCLUSIONS: The authors conclude from these results that antenatal administration of vitamin A attenuates lung hypoplasia in CDH by interfering with early determinants of lung underdevelopment. This finding may have clinical implications because prenatal diagnosis of human CDH commonly occurs after 16 weeks' gestation when late determinants of lung hypoplasia likely predominate.

Animals↗
PubMed2005

The ex utero intrapartum therapy procedure for high-risk fetal lung lesions.

BACKGROUND: Indications for the ex utero intrapartum therapy (EXIT) procedure have expanded to include any fetal anomaly in which resuscitation of the neonate may be compromised. METHODS: We reviewed the medical records of 9 patients after resection of lung lesions during the EXIT procedure. RESULTS: The mean gestational age at EXIT procedure was 35.4 weeks. All lung masses maintained large sizes late into gestation with mean mass volume/head circumference ratio of 2.5 at presentation and 2.2 at EXIT. Seven of 9 fetuses demonstrated hydropic changes (n = 6) and/or polyhydramnios (n = 5), and underwent prenatal intervention including thoracentesis, thoracoamniotic shunt placement, amnioreduction, and/or betamethasone administration. Overall survival after EXIT for lung mass resection was 89%. The average time on placental bypass was 65 minutes. Postnatal complications included reoperation for air leak (n = 1), reoperation for bleeding (n = 1), and death from sepsis and prematurity (n = 1). Venoarterial extracorporeal membrane oxygenation was used in 4 neonates for persistent pulmonary hypertension. Maternal prenatal complications included polyhydramnios (n = 5), preterm labor (n = 4), and chorioamnionitis (n = 1). One mother required perioperative blood transfusion. CONCLUSION: The EXIT procedure allows for controlled resection of large fetal lung lesions at delivery, avoiding acute respiratory decompensation related to mediastinal shift, air trapping, and compression of normal lung.

Adolescent↗
PubMed2005

Reconstitution of hematopoiesis following intrauterine transplantation of stem cells.

In utero hematopoietic stem cell transplantation is an entirely nonmyeloablative approach to achieve mixed hematopoietic chimerism and associated donor-specific tolerance. This chapter provides the rationale and methodologic detail for the administration of stem cells to the "preimmune" mouse fetus by a variety of routes. The development of murine model systems for in utero transplantation has accelerated progress in the field of in utero hematopoietic stem cell transplantation. Creative use of these models should also have experimental application to the fields of fetal gene therapy, stem cell biology, and developmental biology.

Animals↗
PubMed2004

Optimized large-scale production of high titer lentivirus vector pseudotypes.

The goal of the present study was to develop an efficient transient transfection method for large-scale production of high titer lentivirus vector stocks of eight different pseudotypes. The envelope genes used for this purpose were those from VSV-G, Mokola, Rabies, MLV-Ampho, MLV-10A1, LCMV-WE, and LCMV-Arm53b. All envelopes were cloned into phCMV, which yielded lentivirus vector titers one, two, or three orders of magnitude higher than the original plasmids for the Rabies, MLV-10A1, and MLV-Ampho envelopes, respectively. When these newly constructed envelope expression plasmids were used for packaging, treatment with sodium butyrate resulted in almost five-fold increase in titers for some of the pseudotypes, had no effect for others (VSV-G and Rabies), and negatively impacted titers for the LCMV-derived pseudotypes. Production of vectors in serum-free media yielded titers only slightly lower than those obtained in the presence of serum. The efficiency of concentrating vector supernatants by ultracentrifugation or ultrafiltration was compared, with higher recovery efficiencies for the latter method, but the highest titers for most pseudotypes were obtained by ultracentrifugation. The best conditions for each individual pseudotype yielded lentivirus vector stocks with titers above 1 x 10(9) tu/mL for most pseudotypes, and higher than 1 x 10(10) tu/mL for VSV-G.

Cell Line↗
PubMed2004

Heregulin ameliorates the dystrophic phenotype in mdx mice.

Duchenne's muscular dystrophy (DMD) is a fatal neuromuscular disease caused by absence of dystrophin. Utrophin is a chromosome 6-encoded dystrophin-related protein (DRP), sharing functional motifs with dystrophin. Utrophin's ability to compensate for dystrophin during development and when transgenically overexpressed has provided an important impetus for identifying activators of utrophin expression. The utrophin promoter A is transcriptionally regulated in part by heregulin-mediated, extracellular signal-related kinase-dependent activation of the GABP(alpha/beta) transcription factor complex. Therefore, this pathway offers a potential mechanism to modulate utrophin expression in muscle. We tested the ability of heregulin to improve the dystrophic phenotype in the mdx mouse model of DMD. Intraperitoneal injections of a small peptide encoding the epidermal growth factor-like region of heregulin ectodomain for 3 months in vivo resulted in up-regulation of utrophin, a marked improvement in the mechanical properties of muscle as evidenced by resistance to eccentric contraction mediated damage, and a reduction of muscle pathology. The amelioration of dystrophic phenotype by heregulin-mediated utrophin up-regulation offers a pharmacological therapeutic modality and obviates many of the toxicity and delivery issues associated with viral vector-based gene therapy for DMD.

Animals↗
PubMed2004

Acute cardiovascular effects of fetal surgery in the human.

BACKGROUND: Prenatal surgery for congenital anomalies can prevent fetal demise or alter the course of organ development, resulting in a more favorable condition at birth. The indications for fetal surgery continue to expand, yet little is known about the acute sequelae of fetal surgery on the human cardiovascular system. METHODS AND RESULTS: Echocardiography was used to evaluate the heart before, during, and early after fetal surgery for congenital anomalies, including repair of myelomeningocele (MMC, n=51), resection of intrathoracic masses (ITM, n=15), tracheal occlusion for congenital diaphragmatic hernia (CDH, n=13), and resection of sacrococcygeal teratoma (SCT, n=4). Fetuses with MMC all had normal cardiovascular systems entering into fetal surgery, whereas those with ITM, CDH, and SCT all exhibited secondary cardiovascular sequelae of the anomaly present. At fetal surgery, heart rate increased acutely, and combined cardiac output diminished at the time of fetal incision for all groups including those with MMC, which suggests diminished stroke volume. Ventricular dysfunction and valvular dysfunction were identified in all groups, as was acute constriction of the ductus arteriosus. Fetuses with ITM and SCT had the most significant changes at surgery. CONCLUSIONS: Acute cardiovascular changes take place during fetal surgery that are likely a consequence of the physiology of the anomaly and the general effects of surgical stress, tocolytic agents, and anesthesia. Echocardiographic monitoring during fetal surgery is an important adjunct in the management of these patients.

Adult↗
PubMed2004

Favorable neuroblastoma genes and molecular therapeutics of neuroblastoma.

PURPOSE AND EXPERIMENTAL DESIGN: Neuroblastoma (NB) is a common pediatric solid tumor that exhibits a striking clinical bipolarity: favorable and unfavorable. Favorable NB genes (EPHB6, EFNB2, EFNB3, NTRK1, and CD44) are genes whose high-level expression predicts favorable NB outcome, and forced expression of these genes inhibits growth of unfavorable NB cells. In this study, we investigated whether favorable NB gene expression could be augmented in unfavorable NB cells by chemical compounds and whether an increased expression of these genes was associated with suppression of NB growth and metastasis. RESULTS: We found that inhibitors of DNA methylation [5-aza-2'-deoxycytidine (5AdC)], histone deacetylase (HDAC) [4-phenylbutyrate (4PB)], and proteasome (MG262) enhanced the expression of favorable NB genes in NB cell lines and inhibited the growth of these cells in vitro (P < 0.0005). The growth-inhibitory effects of 5AdC and 4PB in vitro were in part due to caspase-dependent cell death and inhibition of DNA synthesis. Administration of 5AdC and/or 4PB also suppressed growth of subcutaneous NB xenografts in nude mice (P < 0.001), which was accompanied by enhanced favorable NB gene expression and an increase in apoptosis. Moreover, 4PB suppressed bone marrow and liver metastases of NB cells in severe combined immunodeficient/Beige mice (P = 0.007 and P = 0.008, respectively). The growth-suppressive activity of HDAC inhibitors on NB was further confirmed by the efficacy of trichostatin A, a potent and specific HDAC inhibitor. CONCLUSIONS: Collectively, these observations further emphasize the link between the elevated favorable NB gene expression and a benign phenotype of NB.

Animals↗
PubMed2004

Prenatally diagnosed giant omphaloceles: short- and long-term outcomes.

OBJECTIVES: To review prenatal findings, short- and long-term outcomes of giant omphaloceles (GO) managed at a single institution (1996-2001). METHODS: Prenatal findings and early postnatal outcomes were retrospectively reviewed. Clinical short- and long-term outcomes were analyzed in eight and five children respectively. Parents and physicians of the children were surveyed by written questionnaires about the children's subsequent health issues. (IRB 2002-2-2683). RESULTS: Seventeen pregnancies with GO were identified: Eight fetuses were live born, four ended in (terminations), two died in utero and three were lost to follow-up. Live-born fetuses had prenatal ascites, extreme levocardia and were delivered by cesarean section at a mean of 37 weeks' gestation with a mean birth weight of 2903 g. All neonates required intubation. Two infants (2/8) died within one year. Four of the six survivors had respiratory insufficiency with a mean ventilation time of 76 days. Respiratory and feeding problems complicated the early neonatal course. Long-term follow-up was available for five patients (mean age of 33.2 months). Asthma, recurrent pulmonary infections, feeding problems, gastroesophageal reflux and failure to thrive were the major problems. CONCLUSIONS: Respiratory and feeding problems were the most common neonatal and long-term medical management issues. Parents need to be counseled prenatally about the probability of multiple surgeries and long hospitalization following birth.

Adolescent↗
PubMed2004

Reproductive outcomes after pregnancy complicated by maternal-fetal surgery.

OBJECTIVE: The reproductive outcomes for women after the pregnancy complicated by maternal-fetal surgery were evaluated to obtain evidence-based information for prenatal risk counseling. STUDY DESIGN: The retrospective review identified 83 women with maternal-fetal surgery from a single institution (1996-2002). These women were sent a consent form and a questionnaire to document postoperative problems, fertility, obstetric outcomes, and psychosocial concerns in pregnancy after the index fetal therapy. Institutional Review Board approval was obtained from Committee for Protection of Human Subjects. RESULTS: The total return rate was 55 (66%). The pregnancy rate was 62% (18% spontaneous abortion, 24% preterm delivery, and 58% term delivery). Complications were reported in 12 of 34 pregnancies (35%), including uterine dehiscence/rupture (12%/6%), cesarean hysterectomy (3%), and antepartum hemorrhage requiring transfusion (9%). CONCLUSION: The reproductive outcome of uterine dehiscence, rupture, and hysterectomy was 12%, 6%, and 3%, respectively, after a pregnancy complicated by maternal-fetal surgery. The uterine rupture rate is similar to the rupture rate after "classical" cesarean section (4%-9%).

Female↗
PubMed2004

In utero stem cell transplantation.

In utero haematopoietic cell transplantation (IUHCT) is a promising approach for the treatment of a variety of genetic disorders. The rationale is to take advantage of normal events during haematopoietic and immunological ontogeny to facilitate allogeneic haematopoietic engraftment. Strategies that will be discussed include the direct achievement of therapeutic levels of donor cell engraftment by IUHCT, the achievement of adequate levels of engraftment to donor-specific tolerance by IUHCT, followed by postnatal non-myeloablative regimens to enhance levels of donor cell engraftment into the therapeutic range. Although in utero haematopoietic cell transplantation has been clinically successful in severe combined immunodeficiency disease (SCID), it has been unsuccessful in target disorders where there is not a selective advantage for donor cells. This chapter presents the recognized barriers to engraftment in the fetus and discusses promising experimental strategies to overcome these barriers.

Female↗
PubMed2004

Complete allogeneic hematopoietic chimerism achieved by in utero hematopoietic cell transplantation and cotransplantation of LLME-treated, MHC-sensitized donor lymphocytes.

OBJECTIVE: In utero hematopoietic cell transplantation (IUHCT) typically achieves low-level mixed hematopoietic chimerism. However, the goal of IUHCT is to achieve therapeutic levels of chimerism. We hypothesized that prenatal adoptive immunotherapy might achieve high-level donor chimerism after IUHCT. MATERIALS AND METHODS: BALB/CE15 fetal mice were transplanted with a mixture of C57BL/6 (B6) T-cell-depleted bone marrow (TCD BM) cells and splenocytes from B6 mice presensitized to BALB/C alloantigen. The splenocytes were preincubated in L-leucyl-L-leucine methyl ester (LLME), to minimize graft vs host disease (GVHD). Recipients were followed after birth for donor cell chimerism and GVHD. RESULTS: Full donor hematopoietic chimerism following a single prenatal transplant was achieved in seven transplanted animals. Fully chimeric animals were healthy, without evidence of GVHD, and maintained their engraftment for the duration of the study (48 weeks). However, the addition of presensitized LLME-treated cells decreased survival until weaning relative to TCD BM alone, suggesting that some animals were lost to acute GVHD. Surviving chimeric animals demonstrated increased frequencies of T-regulatory cell populations in their spleen and BM, suggesting that they had successfully suppressed GVHD, allowing survival. CONCLUSIONS: This study represents "proof in principle" that prenatal immunotherapeutic strategies may achieve complete hematopoietic engraftment across full MHC barriers when combined with IUHCT. However, strategies with greater hematopoietic specificity must be developed prior to consideration of clinical application.

Animals↗
PubMed2004

Mesenchymal stem cells: paradoxes of passaging.

The field of stem cell biology continues to evolve with the ongoing characterization of multiple types of stem cells with their inherent potential for experimental and clinical application. Mesenchymal stem cells (MSC) are one of the most promising stem cell types due to their availability and the relatively simple requirements for in vitro expansion and genetic manipulation. Multiple populations described as "MSCs" have now been isolated from various tissues in humans and other species using a variety of culture techniques. Despite extensive in vitro characterization, relatively little has been demonstrated regarding their in vivo biology and therapeutic potential. Nevertheless, clinical trials utilizing MSCs are currently underway. The aim of this review is to critically analyze the field of MSC biology, particularly with respect to the current paradox between in vitro promise and in vivo efficacy. It is the authors' opinion that until this paradox is better understood, therapeutic applications will remain limited.

Cell Culture Techniques↗
PubMed2004

Sacrococcygeal teratoma: prenatal assessment, fetal intervention, and outcome.

PURPOSE: To understand the natural history and define indications for fetal intervention in sacrococcygeal teratoma (SCT), the authors reviewed all cases of fetal SCT presenting for evaluation. METHODS: Prenatal diagnostic studies including ultrasound scan, magnetic resonance imaging (MRI), echocardiography and pre- and postnatal outcomes were reviewed in 30 cases of SCT that presented between September 1995 and January 2003. RESULTS: The mean gestational age (GA) at presentation was 23.9 weeks (range, 19 to 38.5) with 3 sets of twins (10%). Overall outcomes included 4 terminations, 5 fetal demises, 7 neonatal deaths, and 14 survivors. Significant obstetric complications occurred in 81% of the 26 continuing pregnancies: polyhydramnios (n = 7), oligohydramnios (n = 4), preterm labor (n = 13), preeclampsia (n = 4), gestational diabetes (n = 1), HELLP syndrome (n = 1), and hyperemesis (n = 1). Fetal intervention included cyst aspiration (n = 6), amnioreduction (n = 3), amnioinfusion (n = 1), and open fetal surgical resection (n = 4). Indications for cyst aspiration and amnioreduction were maternal discomfort, preterm labor, and prevention of tumor rupture at delivery. Although 15 SCTs were solid causing risk for cardiac failure, only 4 fetuses met criteria for fetal debulking based on ultrasonographic and echocardiographic evidence of impending high output failure and favorable anatomy at 21, 23.6, 25, and 26 weeks' gestation. Intraoperative events included maternal blood transfusion (n = 1), fetal blood transfusion (n = 2), chorioamniotic membrane separation (n = 2), and fetal arrest requiring successful cardiopulmonary resuscitation (CPR) (n = 1). In the fetal resection group, 3 of 4 survived with mean GA at delivery of 29 weeks (range, 27.6 to 31.7 weeks), mean birth weight of 1.3 kg, hospital stay ranging from 16 to 34 weeks, and follow-up ranging from 20 months to 6 years. Postnatal complications in the fetal surgery group included neonatal death (n = 1, secondary to premature closure of ductus arteriosus with cardiac failure), embolic event (n = 1, resulting in unilateral renal agenesis, jejunal atresia), chronic lung disease (n = 1), and tumor recurrence (n = 1). CONCLUSIONS: For fetal SCT, the rapidity at which cardiac compromise can develop and the high incidence of obstetric complications warrant close prenatal surveillance. Amnioreduction, cyst aspiration, and surgical debulking are potentially life-saving interventions.

Adolescent↗
PubMed2004

Right congenital diaphragmatic hernia: Prenatal assessment and outcome.

PURPOSE: To understand the natural history of right congenital diaphragmatic hernia (CDH), the authors retrospectively reviewed 27 cases of right CDH that presented for prenatal evaluation or postnatal treatment. METHODS: Between 1995 and September 2002, a total of 194 cases of fetal CDH were evaluated and included 22 right-sided defects. The authors reviewed prenatal diagnostic studies (ultrasound scan, magnetic resonance imaging [MRI] echocardiography) and pre- and postnatal outcomes in these 22 cases of right CDH. Five additional cases of right CDH without a prenatal diagnosis were reviewed. RESULTS: The mean gestational age at evaluation was 26.1 weeks. The lung area to head circumference ratio (LHR) ranged from 0.32 to 2.5. In all cases, the fetal liver was herniated into the right chest. Associated anomalies were common. There were no karyotype abnormalities (17 of 22 tested). There were 4 terminations. Nine of the 18 (50%) continuing pregnancies had polyhydramnios, premature rupture of membranes, or preterm labor. The mean gestational age at birth was 36.8 weeks. One patient underwent tracheal occlusion at 27 weeks, and 2 patients died before postnatal repair. Overall survival rate (22 prenatal plus 5 postnatal diagnoses) was 19 of 27 (70%). Postnatal survival rate was 19 of 23 (83%). A Gore-tex (W. L. Gore and Associates, Flagstaff, AZ) patch was utilized in 14 of 21 neonates undergoing surgery. Twelve of 23 (52%) required extracorporeal membrane oxygenation (ECMO) with a 75% survival rate. Significant morbidity occurred in 10 of 19 survivors and included neurologic sequelae in 6 of 19 (32%). CONCLUSIONS: MRI was helpful in the determination of liver position and confirmation of diagnosis. The high incidence of preterm complications, frequent need for ECMO, and high prevalence of comorbidities are indicative of the severity of this CDH population and warrant close prenatal surveillance and delivery at a tertiary care center with ECMO capability.

Extracorporeal Membrane Oxygenation↗
PubMed2003

Long-term transgene expression in cardiac and skeletal muscle following fetal administration of adenoviral or adeno-associated viral vectors in mice.

BACKGROUND: In utero gene transfer may provide advantages for the correction of congenital genetic disorders. In the present study we compare the ability of adenovirus (AdCMVLacZ), and two serotypes of adeno-associated virus (AAVCMVLacZ serotypes 2 and 2/5), to target cardiac and skeletal muscle after prenatal systemic or intramuscular injection in mice and assess the immune response to the vectors. METHODS: Day 14 gestation fetal mice underwent direct intraperitoneal or intramuscular injection of AdCMVLacZ, and AAVCMVLacZ serotypes 2 and 2/5 vectors. Tissues were processed for beta-galactosidase expression in frozen or high-resolution thin plastic sections at early and late time points. Neutralizing antibodies to Ad and AAV were analyzed in separate fetal experimental and neonatal or adult control groups after administration and re-administration of the vectors. RESULTS: A single injection of each vector in utero resulted in sustained expression of beta-galactosidase transgene in skeletal and cardiac muscle. Transgene expression was detected for the length of the study, i.e. 86, 58, and 31 weeks after birth for AdCMVLacZ, and AAVCMVLacZ serotypes 2 and 2/5, respectively. High-level expression in the myocardium was observed independent of the vector or route of administration. Neutralizing antibody responses to AAV and Ad antigens were reduced and long-term expression in muscle was not ablated on postnatal re-administration of vector. CONCLUSIONS: Sustained, high-level cardiac and skeletal muscle transgene expression can be obtained after prenatal gene transfer with each of these vectors. The potential for immune response to viral antigens is altered, but not entirely ablated after in utero exposure.

Adenoviridae↗
PubMed2003

In utero limb salvage: fetoscopic release of amniotic bands for threatened limb amputation.

The natural history of extremity amniotic band syndrome (ABS) is a progression to deformity or amputation. Fetoscopic laser release of amniotic bands in extremity ABS offers the potential to prevent limb amputation. The authors report on 2 patients with isolated extremity ABS who underwent fetoscopic release. Both patients had isolated extremity ABS with compromised extremity perfusion and no other significant structural abnormality diagnosed sonographically. The first patient underwent fetoscopic release of bands of the left wrist, and the second patient underwent lysis of bands around the right wrist and an unsuspected band around the right lower extremity. Both patients had restoration of blood flow by color Doppler to the affected extremity. There were no perioperative complications. In select patients with isolated extremity ABS, early fetoscopic release may prevent amputation and allow improved limb development.

Adult↗
PubMed2003

Congenital high airway obstruction syndrome: natural history and management.

BACKGROUND: Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition with a poorly understood natural history. METHODS: A retrospective review of five patients with CHAOS between 1997 and 2002 was performed. RESULTS: All fetuses had large echogenic lungs, dilated airways, inverted diaphragms, and massive ascites. One fetus with a laryngeal cyst was terminated at 22 weeks. A twin fetus with findings suggestive of a tracheal web had progressive hydrops, which led to fetal demise. The remaining 3 patients delivered via the ex utero intrapartum treatment (EXIT) procedure survived. The first patient tolerated progressive hydrops for 12 weeks in utero. He had tracheal atresia but underwent laryngotracheoplasty successfully. He is the first long-term CHAOS survivor and is speaking at 5 years of age. The 2 patients with relatively stable lung volumes prenatally have laryngeal atresia with a pinpoint posterior laryngeal fistula. Their postnatal clinical courses were much more benign than the first survivor. CONCLUSIONS: The prenatal natural history and postnatal course of CHAOS depends on whether the airway obstruction is complete. The EXIT procedure offers the potential for salvage of this otherwise lethal condition. Hydrops may be well tolerated prenatally for weeks with potential resolution if airway fistulization is present.

Abortion, Eugenic↗