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Abstract
While fetal surgery-and pregnancy termination as a possible therapeutic alternative-have been examined in a number of studies, very few have addressed the issues and tensions that arise when prenatal surgery is considered from the standpoint of Disability Studies. This article will expose these concerns by tracing the medical development of fetal surgery; the arguments for and against prenatal surgery; and the connections between fetal surgery, abortion, and disability rights. Like other dimensions of the life cycle that involve reproduction, prenatal surgery has become highly politicized in the United States which has, to a certain extent, stalled critical discussion. However, the skepticism with which many disability rights advocates and policymakers approach prenatal medical intervention in general has opened a new space for active debate concerning fetal surgery in terms of how it medicalizes pregnancy, pathologizes diversity, contributes to the valuation of life, and emphasizes 'perfect babies' at any cost.
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Pisapia JM, Akbari H, Rozycki M, Goldstein H, Bakas S, Rathore S, Moldenhauer JS, Storm PB, Zarnow DM, Anderson RCE, Heuer GG, Davatzikos C. Use of Fetal Magnetic Resonance Image Analysis and Machine Learning to Predict the Need for Postnatal Cerebrospinal Fluid Diversion in Fetal Ventriculomegaly. JAMA Pediatr 2018; 172:128-135. [PMID: 29255892 PMCID: PMC5796744 DOI: 10.1001/jamapediatrics.2017.3993] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
IMPORTANCE Which children with fetal ventriculomegaly, or enlargement of the cerebral ventricles in utero, will develop hydrocephalus requiring treatment after birth is unclear. OBJECTIVE To determine whether extraction of multiple imaging features from fetal magnetic resonance imaging (MRI) and integration using machine learning techniques can predict which patients require postnatal cerebrospinal fluid (CSF) diversion after birth. DESIGN, SETTING, AND PATIENTS This retrospective case-control study used an institutional database of 253 patients with fetal ventriculomegaly from January 1, 2008, through December 31, 2014, to generate a predictive model. Data were analyzed from January 1, 2008, through December 31, 2015. All 25 patients who required postnatal CSF diversion were selected and matched by gestational age with 25 patients with fetal ventriculomegaly who did not require CSF diversion (discovery cohort). The model was applied to a sample of 24 consecutive patients with fetal ventriculomegaly who underwent evaluation at a separate institution (replication cohort) from January 1, 1998, through December 31, 2007. Data were analyzed from January 1, 1998, through December 31, 2009. EXPOSURES To generate the model, linear measurements, area, volume, and morphologic features were extracted from the fetal MRI, and a machine learning algorithm analyzed multiple features simultaneously to find the combination that was most predictive of the need for postnatal CSF diversion. MAIN OUTCOMES AND MEASURES Accuracy, sensitivity, and specificity of the model in correctly classifying patients requiring postnatal CSF diversion. RESULTS A total of 74 patients (41 girls [55%] and 33 boys [45%]; mean [SD] gestational age, 27.0 [5.6] months) were included from both cohorts. In the discovery cohort, median time to CSF diversion was 6 days (interquartile range [IQR], 2-51 days), and patients with fetal ventriculomegaly who did not develop symptoms were followed up for a median of 29 months (IQR, 9-46 months). The model correctly classified patients who required CSF diversion with 82% accuracy, 80% sensitivity, and 84% specificity. In the replication cohort, the model achieved 91% accuracy, 75% sensitivity, and 95% specificity. CONCLUSION AND RELEVANCE Image analysis and machine learning can be applied to fetal MRI findings to predict the need for postnatal CSF diversion. The model provides prognostic information that may guide clinical management and select candidates for potential fetal surgical intervention.
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Affiliation(s)
- Jared M. Pisapia
- Department of Neurosurgery, University of Pennsylvania, Philadelphia,Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia
| | - Hamed Akbari
- Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia
| | - Martin Rozycki
- Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia
| | - Hannah Goldstein
- Department of Neurosurgery, Columbia University Medical Center, New York, New York
| | - Spyridon Bakas
- Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia
| | - Saima Rathore
- Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia
| | - Julie S. Moldenhauer
- Center for Fetal Diagnosis and Treatment, Special Delivery Unit, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Phillip B. Storm
- Department of Neurosurgery, University of Pennsylvania, Philadelphia,Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Deborah M. Zarnow
- Division of Neuroradiology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | | | - Gregory G. Heuer
- Department of Neurosurgery, University of Pennsylvania, Philadelphia,Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Christos Davatzikos
- Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia
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Pisapia JM, Sinha S, Zarnow DM, Johnson MP, Heuer GG. Fetal ventriculomegaly: Diagnosis, treatment, and future directions. Childs Nerv Syst 2017; 33:1113-1123. [PMID: 28510072 DOI: 10.1007/s00381-017-3441-y] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 04/28/2017] [Indexed: 11/25/2022]
Abstract
Fetal ventriculomegaly (VM) refers to the enlargement of the cerebral ventricles in utero. It is associated with the postnatal diagnosis of hydrocephalus. VM is clinically diagnosed on ultrasound and is defined as an atrial diameter greater than 10 mm. Because of the anatomic detailed seen with advanced imaging, VM is often further characterized by fetal magnetic resonance imaging (MRI). Fetal VM is a heterogeneous condition with various etiologies and a wide range of neurodevelopmental outcomes. These outcomes are heavily dependent on the presence or absence of associated anomalies and the direct cause of the ventriculomegaly rather than on the absolute degree of VM. In this review article, we discuss diagnosis, work-up, counseling, and management strategies as they relate to fetal VM. We then describe imaging-based research efforts aimed at using prenatal data to predict postnatal outcome. Finally, we review the early experience with fetal therapy such as in utero shunting, as well as the advances in prenatal diagnosis and fetal surgery that may begin to address the limitations of previous therapeutic efforts.
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Affiliation(s)
- Jared M Pisapia
- Department of Neurosurgery, University of Pennsylvania, 3400 Spruce Street, 3rd Floor Silverstein Pavilion, Philadelphia, PA, 19104, USA.
| | - Saurabh Sinha
- Department of Neurosurgery, University of Pennsylvania, 3400 Spruce Street, 3rd Floor Silverstein Pavilion, Philadelphia, PA, 19104, USA
| | - Deborah M Zarnow
- Division of Neuroradiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.,The Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Mark P Johnson
- The Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Gregory G Heuer
- Department of Neurosurgery, University of Pennsylvania, 3400 Spruce Street, 3rd Floor Silverstein Pavilion, Philadelphia, PA, 19104, USA.,The Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Philadelphia, PA, USA.,Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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Emery SP, Greene S, Hogge WA. Fetal Therapy for Isolated Aqueductal Stenosis. Fetal Diagn Ther 2015; 38:81-5. [PMID: 25997519 DOI: 10.1159/000382015] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Accepted: 03/27/2015] [Indexed: 11/19/2022]
Abstract
Aqueductal stenosis (AS) is a form of noncommunicating hydrocephalus, which causes increased intracranial pressure secondary to obstruction of the aqueduct of Sylvius. Relief of intracranial pressure in the fetus by ventriculoamniotic shunting may diminish or even prevent permanent neurologic injury. Shunting was attempted in the 1980s but was abandoned due to technical difficulties. Given the advances in prenatal diagnosis and fetal intervention over the last 3 decades, we believe that an evidence-based reevaluation of the option is timely and appropriate. The aim of this review article is to discuss the clinical significance of the diagnosis of AS, current management strategies, current diagnostic capabilities, new shunt technology, and barriers to progress. Finally, we will advance a research agenda that will provide evidence-based management recommendations.
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Affiliation(s)
- Stephen P Emery
- Departments of Obstetrics, Gynecology and Reproductive Sciences, The University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA
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Lankford L, Selby T, Becker J, Ryzhuk V, Long C, Farmer D, Wang A. Early gestation chorionic villi-derived stromal cells for fetal tissue engineering. World J Stem Cells 2015; 7:195-207. [PMID: 25621120 PMCID: PMC4300931 DOI: 10.4252/wjsc.v7.i1.195] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 11/04/2014] [Accepted: 11/07/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the potential for early gestation placenta-derived mesenchymal stromal cells (PMSCs) for fetal tissue engineering. METHODS PMSCs were isolated from early gestation chorionic villus tissue by explant culture. Chorionic villus sampling (CVS)-size tissue samples (mean = 35.93 mg) were used to test the feasibility of obtaining large cell numbers from CVS within a clinically relevant timeframe. We characterized PMSCs isolated from 6 donor placentas by flow cytometry immunophenotyping, multipotency assays, and through immunofluorescent staining. Protein secretion from PMSCs was examined using two cytokine array assays capable of probing for over 70 factors in total. Delivery vehicle compatibility of PMSCs was determined using three common scaffold systems: fibrin glue, collagen hydrogel, and biodegradable nanofibrous scaffolds made from a combination of polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA). Viral transduction of PMSCs was performed using a Luciferase-GFP-containing lentiviral vector and efficiency of transduction was tested by fluorescent microscopy and flow cytometry analysis. RESULTS We determined that an average of 2.09 × 10(6) (SD ± 8.59 × 10(5)) PMSCs could be obtained from CVS-size tissue samples within 30 d (mean = 27 d, SD ± 2.28), indicating that therapeutic numbers of cells can be rapidly expanded from very limited masses of tissue. Immunophenotyping by flow cytometry demonstrated that PMSCs were positive for MSC markers CD105, CD90, CD73, CD44, and CD29, and were negative for hematopoietic and endothelial markers CD45, CD34, and CD31. PMSCs displayed trilineage differentiation capability, and were found to express developmental transcription factors Sox10 and Sox17 as well as neural-related structural proteins NFM, Nestin, and S100β. Cytokine arrays revealed a robust and extensive profile of PMSC-secreted cytokines and growth factors, and detected 34 factors with spot density values exceeding 10(3). Detected factors had widely diverse functions that include modulation of angiogenesis and immune response, cell chemotaxis, cell proliferation, blood vessel maturation and homeostasis, modulation of insulin-like growth factor activity, neuroprotection, extracellular matrix degradation and even blood coagulation. Importantly, PMSCs were also determined to be compatible with both biological and synthetic material-based delivery vehicles such as collagen and fibrin hydrogels, and biodegradable nanofiber scaffolds made from a combination of PLA and PLGA. Finally, we demonstrated that PMSCs can be efficiently transduced (> 95%) with a Luciferase-GFP-containing lentiviral vector for future in vivo cell tracking after transplantation. CONCLUSION Our findings indicate that PMSCs represent a unique source of cells that can be effectively utilized for in utero cell therapy and tissue engineering.
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Affiliation(s)
- Lee Lankford
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Taryn Selby
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - James Becker
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Volodymyr Ryzhuk
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Connor Long
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Diana Farmer
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
| | - Aijun Wang
- Lee Lankford, Taryn Selby, James Becker, Volodymyr Ryzhuk, Connor Long, Diana Farmer, Aijun Wang, Department of Surgery, University of California, Davis Health System, Sacramento, CA 95817, United States
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Ikeako L, Ezegwui H, Onwudiwe E, Enwereji J. Attitude of expectant mothers on the use of ultrasound in pregnancy in a tertiary institution in South East of Nigeria. Ann Med Health Sci Res 2014; 4:949-53. [PMID: 25506492 PMCID: PMC4250997 DOI: 10.4103/2141-9248.144923] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background: With the world-wide availability of ultrasound services even in the developing countries, routine ultrasonography in pregnancy remains a controversial issue. However, in this era of reproductive health right and evidence-based medicine, the views of women need to be ascertained. Aims: The aim is to assess the attitude of antenatal women toward sonography in pregnancy. Subjects and Methods: A descriptive self-administered questionnaire-based cross-sectional study using 208 women that booked for antenatal care from January 1, 2009 to June 30, 2009 at the University of Nigeria Teaching Hospital, Enugu. Results: The number of respondents who had ultrasonography in their previous pregnancies was 58.7% (122/208). Although many reasons were given for personal ultrasound requests, 19.7% (24/122) of the women who had obstetric scan in their previous pregnancies thought it was a normal booking test done for every pregnant woman. When compared with other booking investigations, 60.1% (125/208), mainly civil servants .expressed the views that ultrasound in pregnancy is costly, while 24.4% (59/208) felt it is cheap, 9.1% (19/208) said it is very costly, while the remaining 2.4% (5/208) thought it is not affordable. Apart from visualizing the images of their babies, 17.8% (37/208) of the cases wanted to know the sexes of their babies while 15.4% (32/208) was for determination of fetal position. Out of 110, 52.9% (110/208) were of the opinion that women can decide when to request for sonography. Conclusion: The attitude of Nigerian women to sonography is good. Majority of them request ultrasound for fetal observation and gender determination.
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Affiliation(s)
- Lc Ikeako
- Department of Obstetrics and Gynecology, Anambra State University Teaching Hospital, Amaku, Awka, Nigeria
| | - Hu Ezegwui
- Department of Obstetrics and Gynecology, University of Nigeria Teaching Hospital, Enugu, Nigeria
| | - E Onwudiwe
- Department of Obstetrics and Gynecology, University of Nigeria Teaching Hospital, Enugu, Nigeria
| | - Jo Enwereji
- Department of Obstetrics and Gynecology, University of Nigeria Teaching Hospital, Enugu, Nigeria
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Saadai P, Lee TH, Bautista G, Gonzales KD, Nijagal A, Busch MP, Kim CJ, Romero R, Lee H, Hirose S, Rand L, Miniati D, Farmer DL, MacKenzie TC. Alterations in maternal-fetal cellular trafficking after fetal surgery. J Pediatr Surg 2012; 47:1089-94. [PMID: 22703775 PMCID: PMC3377979 DOI: 10.1016/j.jpedsurg.2012.03.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2012] [Accepted: 03/05/2012] [Indexed: 01/17/2023]
Abstract
BACKGROUND/PURPOSE Bidirectional trafficking of cells between the mother and the fetus is routine in pregnancy and a component of maternal-fetal tolerance. Changes in fetal-to-maternal cellular trafficking have been reported in prenatal complications, but maternal-to-fetal trafficking has never been studied in the context of fetal intervention. We hypothesized that patients undergoing open fetal surgery would have altered maternal-fetal cellular trafficking. METHODS Cellular trafficking was analyzed in patients with myelomeningocele (MMC) who underwent open fetal surgical repair (n = 5), patients with MMC who had routine postnatal repair (n = 6), and healthy control healthy patients (n = 9). As an additional control for the fetal operation, trafficking was also analyzed in patients who were delivered by an ex utero intrapartum treatment procedure (n = 6). Microchimerism in maternal and cord blood was determined using quantitative real-time polymerase chain reaction for nonshared alleles. RESULTS Maternal-to-fetal trafficking was significantly increased in patients who underwent open fetal surgery for MMC compared with healthy controls, patients who underwent postnatal MMC repair, and patients who underwent ex utero intrapartum treatment. There were no differences in fetal-to-maternal cell trafficking among groups. CONCLUSION Patients undergoing open fetal surgery for MMC have elevated levels of maternal microchimerism. These results suggest altered trafficking and/or increased proliferation of maternal cells in fetal blood and may have important implications for preterm labor.
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Affiliation(s)
- Payam Saadai
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA 94143-0570, USA.
| | - Tzong-Hae Lee
- Blood Systems Research Institute, San Francisco, CA, USA
| | - Geoanna Bautista
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
| | - Kelly D. Gonzales
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
| | - Amar Nijagal
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
| | | | - CJ Kim
- Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, Michigan, USA
| | - Roberto Romero
- Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, Michigan, USA
| | - Hanmin Lee
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
| | - Shinjiro Hirose
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
| | - Larry Rand
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
| | - Douglas Miniati
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
| | - Diana L. Farmer
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
| | - Tippi C. MacKenzie
- Division of Pediatric Surgery and Fetal Treatment Center, Department of Surgery, University of California, San Francisco, CA, USA
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Farrell J, Howell LJ. An Overview of Surgical Techniques, Research Trials, and Future Directions of Fetal Therapy. J Obstet Gynecol Neonatal Nurs 2012; 41:419-25. [DOI: 10.1111/j.1552-6909.2012.01356.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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