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  1. Article ; Online: Noninvasive prenatal testing: from aneuploidy to single genes.

    Guseh, Stephanie H

    Human genetics

    2019  Volume 139, Issue 9, Page(s) 1141–1148

    Abstract: Noninvasive prenatal testing has undergone rapid advances in the last few years. Although researchers have long known about circulating pregnancy-based cell-free fragments of DNA in maternal plasma, it was the introduction of massively parallel ... ...

    Abstract Noninvasive prenatal testing has undergone rapid advances in the last few years. Although researchers have long known about circulating pregnancy-based cell-free fragments of DNA in maternal plasma, it was the introduction of massively parallel sequencing that allowed noninvasive prenatal testing to become a widely used clinical test. This review will begin with an in-depth analysis of the use of noninvasive prenatal testing for aneuploidy, including common causes for inaccurate and/or discordant results. It will also review the ongoing expansion of noninvasive prenatal testing to include copy number variants and select single-gene disorders. Finally, integrated throughout the review is a comparison of noninvasive prenatal testing to more traditional screening methods along with some medical and ethical implications of the widespread use of this new technology.
    MeSH term(s) Aneuploidy ; Cell-Free Nucleic Acids/blood ; Cell-Free Nucleic Acids/genetics ; DNA/genetics ; False Negative Reactions ; False Positive Reactions ; Female ; Genetic Diseases, Inborn/diagnosis ; Genetic Diseases, Inborn/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Noninvasive Prenatal Testing/methods ; Pregnancy ; Prenatal Diagnosis/methods
    Chemical Substances Cell-Free Nucleic Acids ; DNA (9007-49-2)
    Language English
    Publishing date 2019-09-25
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 223009-4
    ISSN 1432-1203 ; 0340-6717
    ISSN (online) 1432-1203
    ISSN 0340-6717
    DOI 10.1007/s00439-019-02061-1
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  2. Article ; Online: Postnatal genetic testing on cord blood for prenatally identified high-probability cases.

    Adams, Sophie / Llorin, Hannah / Dobson, Lori J / Studwell, Courtney / Wilkins-Haug, Louise / Guseh, Stephanie / Gray, Kathryn J

    Prenatal diagnosis

    2023  Volume 43, Issue 9, Page(s) 1120–1131

    Abstract: Objective: To evaluate the utility of postnatal genetic testing on umbilical cord blood (CB) for prenatally identified high-probability fetuses.: Method: CB for genetic testing was offered to individuals who met one of the following criteria: (i) ... ...

    Abstract Objective: To evaluate the utility of postnatal genetic testing on umbilical cord blood (CB) for prenatally identified high-probability fetuses.
    Method: CB for genetic testing was offered to individuals who met one of the following criteria: (i) fetal anomaly, (ii) positive non-invasive prenatal screening by cfDNA or biochemical analysis, or (iii) family history. Individuals with diagnostic testing, but not microarray, were also included when recommended by society guidelines. CB was collected at Brigham and Women's and Emerson Hospitals between 2016 and 2021.
    Results: 448 individuals consented for cord blood testing (370 (82.6%) for fetal anomalies, 51 (11.4%) for high-probability cfDNA, and 27 (6.0%) for family history) and a total of 393 (87.7%) samples were analyzed. Genetic testing yielded a diagnosis in 92 (23.4%) neonates by karyotype (n = 37), chromosomal microarray (CMA) (n = 32), and other molecular analysis (n = 23). Testing averaged 10.3 days (range 1-118 days). 68 (73.9%) diagnoses potentially impacted neonatal management. MCC could not be definitively excluded in only 1.4% (6/418) of samples.
    Conclusion: Prenatal identification of high-probability fetuses and genetic testing on CB facilitates timely genetic diagnoses and neonatal management. Testing provides reassurance and reduces a postnatal diagnostic odyssey for high-probability neonates.
    MeSH term(s) Infant, Newborn ; Pregnancy ; Humans ; Female ; Fetal Blood ; Genetic Testing ; Fetus ; Cell-Free Nucleic Acids ; Probability
    Chemical Substances Cell-Free Nucleic Acids
    Language English
    Publishing date 2023-04-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 82031-3
    ISSN 1097-0223 ; 0197-3851
    ISSN (online) 1097-0223
    ISSN 0197-3851
    DOI 10.1002/pd.6352
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  3. Article ; Online: Fetal cardiac intervention-Perspectives from a single center.

    Guseh, Stephanie H / Friedman, Kevin G / Wilkins-Haug, Louise E

    Prenatal diagnosis

    2020  Volume 40, Issue 4, Page(s) 415–423

    Abstract: Fetal cardiac intervention was first proposed in the early 1990s to impact cardiac development and survival of fetuses with fetal aortic stenosis and evolving hypoplastic left heart syndrome (HLHS). Although initial attempts of fetal aortic valvuloplasty ...

    Abstract Fetal cardiac intervention was first proposed in the early 1990s to impact cardiac development and survival of fetuses with fetal aortic stenosis and evolving hypoplastic left heart syndrome (HLHS). Although initial attempts of fetal aortic valvuloplasty were unsuccessful and carried a high rate of morbidity and mortality, our collaborative group at the Brigham and Women's Hospital and Boston Children's Hospital have reinvigorated the procedure using improvements in imaging, anesthesia, balloon catheters, and surgical techniques. Two decades of experience have now allowed us to document the safety of in utero intervention and to achieve a better understanding of the impact of midgestation intervention on developing HLHS. Research into underlying genetics, predictive biomarkers, and ways to incorporate stem cell technology will hopefully allow us to further refine the procedure to most benefit children with this historically lethal disease.
    MeSH term(s) Aortic Valve Stenosis/complications ; Aortic Valve Stenosis/therapy ; Balloon Valvuloplasty ; Female ; Fetal Heart/diagnostic imaging ; Fetal Therapies ; Humans ; Hypoplastic Left Heart Syndrome/etiology ; Hypoplastic Left Heart Syndrome/prevention & control ; Pregnancy ; Ultrasonography, Prenatal
    Language English
    Publishing date 2020-01-09
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 82031-3
    ISSN 1097-0223 ; 0197-3851
    ISSN (online) 1097-0223
    ISSN 0197-3851
    DOI 10.1002/pd.5631
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  4. Article ; Online: High-Resolution and Noninvasive Fetal Exome Screening.

    Brand, Harrison / Whelan, Christopher W / Duyzend, Michael / Lemanski, John / Salani, Monica / Hao, Stephanie P / Wong, Isaac / Valkanas, Elise / Cusick, Caroline / Genetti, Casie / Dobson, Lori / Studwell, Courtney / Gianforcaro, Kathleen / Wilkins-Haug, Louise / Guseh, Stephanie / Currall, Benjamin / Gray, Kathryn / Talkowski, Michael E

    The New England journal of medicine

    2023  Volume 389, Issue 21, Page(s) 2014–2016

    MeSH term(s) Female ; Humans ; Pregnancy ; Exome ; Genetic Testing/methods ; Prenatal Diagnosis/methods ; Exome Sequencing/methods ; Fetal Diseases/genetics ; Genetic Diseases, Inborn/diagnosis ; Genetic Diseases, Inborn/genetics
    Language English
    Publishing date 2023-12-07
    Publishing country United States
    Document type Letter
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2216144
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  5. Article ; Online: Counseling for personal health implications identified during reproductive genetic carrier screening.

    Gbur, Samantha / Mauney, Logan / Gray, Kathryn J / Wilkins-Haug, Louise / Guseh, Stephanie

    Prenatal diagnosis

    2021  Volume 41, Issue 11, Page(s) 1460–1466

    Abstract: Objective: Preconception and prenatal carrier screening is designed to provide reproductive risk information, but carriers for some autosomal recessive or X-linked conditions also have personal health risks. This study investigated the prevalence of and ...

    Abstract Objective: Preconception and prenatal carrier screening is designed to provide reproductive risk information, but carriers for some autosomal recessive or X-linked conditions also have personal health risks. This study investigated the prevalence of and inclusion of personal health implications in pre- and post-test counseling.
    Methods: Twelve genetic conditions with personal health risks for carriers included on carrier screening panels but not otherwise screened routinely were identified (e.g., Gaucher disease with Parkinson's disease risk). A retrospective review was performed of patients with a positive carrier screen for one of these conditions at our center from 2012 to 2019.
    Results: Of 6147 individuals that had carrier screening for one of the twelve conditions, 96 (1.56%) did not report a known family history and screened positive for one of the conditions. Testing was ordered largely by reproductive endocrinologists (51.0%) and genetic counselors (35.4%). Most individuals did not receive pre- (96.8%) or post-test (64.6%) counseling about personal health risks. Post-test counseling was performed principally by genetic counselors (97.1%). For carriers of conditions with guidelines for specialist referral, most individuals (75.9%) were referred.
    Conclusion: Expanded genetic carrier screening increasingly identifies individuals with personal health implications, but patients are frequently not counseled before or after testing. These findings stress the importance of developing guidelines for practitioners about expanded carrier screening counseling and follow-up.
    MeSH term(s) Adult ; Female ; Genetic Carrier Screening/methods ; Genetic Carrier Screening/statistics & numerical data ; Genetic Counseling/methods ; Genetic Counseling/psychology ; Genetic Counseling/statistics & numerical data ; Humans ; Male ; Pregnancy ; Prenatal Diagnosis/methods ; Prenatal Diagnosis/psychology ; Prenatal Diagnosis/statistics & numerical data ; Retrospective Studies
    Language English
    Publishing date 2021-09-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 82031-3
    ISSN 1097-0223 ; 0197-3851
    ISSN (online) 1097-0223
    ISSN 0197-3851
    DOI 10.1002/pd.6033
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  6. Article ; Online: Transuterine Ultrasound-Guided Fetal Embolization of Vein of Galen Malformation, Eliminating Postnatal Pathophysiology.

    Orbach, Darren B / Wilkins-Haug, Louise E / Benson, Carol B / Tworetzky, Wayne / Rangwala, Shivani D / Guseh, Stephanie H / Gately, Nicole K / Stout, Jeffrey N / Mizrahi-Arnaud, Arielle / See, Alfred P

    Stroke

    2023  Volume 54, Issue 6, Page(s) e231–e232

    MeSH term(s) Humans ; Vein of Galen Malformations/diagnostic imaging ; Vein of Galen Malformations/therapy ; Cerebral Veins/diagnostic imaging ; Heart Failure/therapy ; Ultrasonography ; Embolization, Therapeutic ; Ultrasonography, Interventional
    Language English
    Publishing date 2023-05-04
    Publishing country United States
    Document type Research Support, Non-U.S. Gov't ; Letter
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.123.043421
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  7. Article ; Online: Single gene non-invasive prenatal screening for autosomal dominant conditions in a high-risk cohort.

    Adams, Sophie / Llorin, Hannah / Maher, Olivia / Dean, Meghan / Dobson, Lori J / Gbur, Sam / Foster, Judith / McElhinney, Sarah / Evans, Chloe / Kelly, Hannah / Wilkins-Haug, Louise / Guseh, Stephanie / Gray, Kathryn J

    Prenatal diagnosis

    2023  Volume 43, Issue 9, Page(s) 1110–1119

    Abstract: Purpose: To determine the utility of single gene non-invasive prenatal screening (NIPS-SGD) in a high-risk reproductive genetics clinic.: Methods: A clinical pilot for NIPS-SGD was conducted from March 2020 to November 2021. A NIPS-SGD panel ... ...

    Abstract Purpose: To determine the utility of single gene non-invasive prenatal screening (NIPS-SGD) in a high-risk reproductive genetics clinic.
    Methods: A clinical pilot for NIPS-SGD was conducted from March 2020 to November 2021. A NIPS-SGD panel assessing pathogenic variants in 30 genes was offered to pregnant individuals for the following indications: (1) advanced sperm age ≥40 years, (2) nuchal translucency (NT) ≥ 3.5 mm, (3) fetal anomaly, or (4) family history of a condition covered by the panel. Diagnostic testing was offered concurrently.
    Results: NIPS-SGD was ordered for 253 individuals: 88 (34.8%) for fetal anomalies, 96 (37.9%) for advanced sperm age, 37 (14.6%) for increased NT, and 5 (2.0%) for family history. Among 228 (90.1%) completed tests, 8 (3.5%) were positive. Diagnostic testing for 78 individuals revealed no false positive or negative results. Of 41 (25.9%) individuals who received a molecular diagnosis, 34 (82.9%) were outside the scope of NIPS-SGD. Positive NIPS-SGD altered medical management in five cases.
    Conclusions: NIPS-SGD in a high-risk population can lead to earlier prenatal diagnosis, enhanced surveillance, and targeted genetic analysis, but should not replace clinically indicated diagnostic testing. Potential incidental findings include parental diagnoses and misattributed parentage.
    MeSH term(s) Pregnancy ; Female ; Male ; Humans ; Adult ; Semen ; Prenatal Diagnosis/methods ; Nuchal Translucency Measurement ; Aneuploidy
    Language English
    Publishing date 2023-04-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 82031-3
    ISSN 1097-0223 ; 0197-3851
    ISSN (online) 1097-0223
    ISSN 0197-3851
    DOI 10.1002/pd.6351
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  8. Article ; Online: Call to action: prioritizing delivery room care for neonates with critical congenital heart disease.

    Thomas, Alyssa R / Levy, Philip T / Donofrio, Mary T / Law, Brenda / Joynt, Chloe / Gupta, Ruby / Elshenawy, Summer / Reed, Danielle / Pavlek, Leeann R / Shepherd, Jennifer / Gowda, Sharada H / Johnson, Beth Ann / Abdulhayoglu, Elisa / Valencia, Eleonore / Guseh, Stephanie / Ball, Molly K / Ali, Noorjahan

    Journal of perinatology : official journal of the California Perinatal Association

    2023  Volume 44, Issue 3, Page(s) 321–324

    MeSH term(s) Infant, Newborn ; Pregnancy ; Humans ; Female ; Delivery Rooms ; Heart Defects, Congenital/therapy
    Language English
    Publishing date 2023-11-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645021-0
    ISSN 1476-5543 ; 0743-8346
    ISSN (online) 1476-5543
    ISSN 0743-8346
    DOI 10.1038/s41372-023-01828-9
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  9. Article ; Online: Technically successful fetal aortic valvuloplasty acutely improves left heart output.

    Asrani, Priyanka P / Gellis, Laura A / Schidlow, David / Callahan, Ryan / Porras, Diego / Wilkins-Haug, Louise / Guseh, Stephanie / Tworetzky, Wayne / Friedman, Kevin G

    Prenatal diagnosis

    2022  Volume 42, Issue 11, Page(s) 1466–1470

    MeSH term(s) Aortic Valve Stenosis/surgery ; Balloon Valvuloplasty ; Fetal Heart/diagnostic imaging ; Fetal Heart/surgery ; Humans ; Treatment Outcome
    Language English
    Publishing date 2022-09-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 82031-3
    ISSN 1097-0223 ; 0197-3851
    ISSN (online) 1097-0223
    ISSN 0197-3851
    DOI 10.1002/pd.6240
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  10. Article ; Online: Hemodynamic and anatomic changes after fetal aortic valvuloplasty are associated with procedural success and postnatal biventricular circulation.

    Bradford, Victoria R / Tworetzky, Wayne / Callahan, Ryan / Wilkins-Haug, Louise E / Benson, Carol B / Porras, Diego / Guseh, Stephanie H / Lu, Minmin / Sleeper, Lynn A / Gellis, Laura / Friedman, Kevin G

    Prenatal diagnosis

    2022  Volume 42, Issue 10, Page(s) 1312–1322

    Abstract: Background: There are minimal data characterizing the trajectory of left heart growth and hemodynamics following fetal aortic valvuloplasty (FAV).: Methods: This retrospective study included patients who underwent FAV between 2000 and 2019, with ... ...

    Abstract Background: There are minimal data characterizing the trajectory of left heart growth and hemodynamics following fetal aortic valvuloplasty (FAV).
    Methods: This retrospective study included patients who underwent FAV between 2000 and 2019, with echocardiograms performed pre-FAV, immediately post-FAV, and in late gestation.
    Results: Of 118 fetuses undergoing FAV, 106 (90%) underwent technically successful FAV, of which 55 (52%) had biventricular circulation. Technically successful FAV was associated with improved aortic valve growth (p < 0.001), sustained antegrade aortic arch (AoA) flow (p = 0.02), improved mitral valve (MV) inflow pattern (p = 0.002), and favorable patent foramen ovale (PFO) flow pattern (p = 0.004) from pre-FAV to late gestation. Compared to patients with univentricular outcome, patients with biventricular outcome had less decrement in size of the left ventricle (LV) (p < 0.001) and aortic valve (p = 0.005), as well as more physiologic PFO flow (p < 0.001) and antegrade AoA flow (p < 0.001) from pre-FAV to late gestation. In multivariable analysis, echocardiographic predictors of biventricular outcome were less decline in LV end diastolic dimension (p < 0.001), improved PFO flow (p = 0.004), and sustained antegrade AoA flow (p = 0.002) from pre-FAV to late gestation.
    Conclusion: Stabilization of left heart growth and improved hemodynamics following successful FAV through late gestation are associated with postnatal biventricular circulation.
    MeSH term(s) Aortic Valve Stenosis/complications ; Balloon Valvuloplasty/methods ; Female ; Fetus ; Hemodynamics ; Humans ; Pregnancy ; Retrospective Studies ; Treatment Outcome
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 82031-3
    ISSN 1097-0223 ; 0197-3851
    ISSN (online) 1097-0223
    ISSN 0197-3851
    DOI 10.1002/pd.6216
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