Implications of Maternal 45,X Mosaicism as a Secondary Genomic Finding Following Cell-Free DNA Sequencing During Pregnancy: A Deep Phenotype Study

NCT05548881 | Withdrawn

• 2 other identifiers: 10000137000137-CH
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Mosaicism is a condition in which cells within the same person have a different genetic makeup. Sometimes, a type of mosaicism called 45,X may not be discovered in a woman until she undergoes routine tests during pregnancy. Little is known about how 45,X mosaicism may affect a person s long-term health. Objective: This natural history study will look for health risks in people with 45,X mosaicism. Eligibility: People aged 18 to 99 years who during pregnancy were found to have 45,X mosaicism. Healthy volunteers are also needed. Design: Participants will stay in the clinic for 2 days. They will have many tests: A physical exam, including measurements of the body. A gynecological exam, including genital measurements. Photos may be taken, with consent. Blood tests, with blood drawn over an 8-week period. An oral glucose test for diabetes may also be done. Tests of heart function. Participants will have small stickers attached to wires place on their chest, arms, and legs. Hearing tests. Ultrasound exams, which use echoing sound waves to create images of organs such as the heart and kidneys. Imaging scans including x-rays, MRI, and DXA. The DXA uses x-rays to measure bone density and body fat. Other types of scans will capture images of the liver. Participants will complete 4 surveys with questions about their sexual function, anxiety, depression, and health. Participants may remain in the study for 20 years. For 5 years, they will have a yearly follow-up by phone or email. They may have follow-up visits at the clinic every 5 years.

Conditions

Cardiovascular Phenotype; Metabolic Phenotype; Hypertensive Disease; Psychological Phenotype; Audio

Keywords

Fetal Neonatal; Maternal; Turner Syndrome; Chromosomes; reproductive; Natural History

Outcome Measures

Primary Outcomes (1)

• Hypertension

  Evaluation of hypertension as defined in 2017 by the American College of Cardiology/American Heart Association (ACC/AHA): Normal blood pressure - Systolic \<120 mmHg and diastolic \<80 mmHg

  5 Years

Study Arms (2)

Group 1

Women who have submitted clinical samples for prenatal aneuploidy screening test with the finding of X mosaicism

Group 2 (Control)

Control group of Female volunteers of appropriate age, ethnicity, BMI, SES and parity

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women who have submitted clinical samples for prenatal aneuploidy screening test with the finding of X mosaicism will be recruited from laboratories that offer cell-free DNA testing during pregnancy as well as nation-wide obstetricians and maternal-fetal-medicine specialists Potential participants are likely to be referred from specialists who care for them or will find the protocol through an internet search A control group of volunteers of appropriate age, ethnicity, BMI, SES and parity will be recruited using resources of the NIH Office of Patient Recruitment (OPR) and AlescoData and will be a matched to study participants.

You may qualify if:

• Individuals of all races/ethnicities are eligible to participate.
• Individuals assigned female sex at birth ages \>=18 to \<= 99 years old who have not undergone medical and/or surgical transgender treatment
• Suspected maternal 45,X mosaicism as a secondary genomic finding following cfDNA sequencing during pregnancy
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Ability to read and comprehend written and verbal English as the documents required for the study have not been translated for non-English speaking speakers.
• Individuals assigned female sex at birth ages \>=18 to \<= 99 years old who have not undergone medical and/or surgical transgender treatment
• Good general health. In general, subjects should take no medications. The use of over the counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication prior to study entry may be still eligible.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Ability to read and comprehend written and verbal English as the documents required for the study have not been translated for non-English speaking speakers.

You may not qualify if:

• An individual who meets any of the following criteria at screening or baseline will be excluded from participation in this study:
• Male and transfemale individuals
• Individuals with significant medical comorbidities (e.g. NYHA Class III or IV heart failure, or CKD Stage 3b or worse (eGFR \< 60 mL/min/1.73 m2), or American Society of Anesthesiologists Physical Status Class 3 or above) or other serious disorders at the discretion of the investigators.
• Individuals who have current substance abuse or a DSM 5 Axis I psychiatric disorder or DSM Axis II Mental Retardation diagnosis that in the opinion of the investigators would impede competence, compliance, or participation in the study
• Male and transfemale individuals
• Individuals with significant medical comorbidities (e.g. NYHA Class III or IV heart failure, or CKD Stage 3b or worse (eGFR \< 60 mL/min/1.73 m2), or American Society of Anesthesiologists Physical Status Class 3 or above) or other serious disorders at the discretion of the investigators.
• For females of reproductive potential: use of oral contraceptive pills, contraceptive patch, contraceptive vaginal ring within the past 3 months; use of depo medroxyprogesterone within the past 6 months; use of the etonorgestrel contraceptive implant within the past 1 month.
• Individuals who are pregnant, planning to become pregnant, currently nursing an infant, or have irregular menses, defined as cycles less than 21 days or greater than 45 days in premenopausal women.
• Previous history of the following: malignancy, chemotherapy, radiation therapy, primary ovarian insufficiency, galactosemia.
• Individuals who have current substance abuse or a DSM 5 Axis I psychiatric disorder or DSM Axis II Mental Retardation diagnosis that in the opinion of the investigators would impede competence, compliance, or participation in the study.
• Current use of tobacco or nicotine (eg. Nicotine patch, e-cigarette) products.
• Individuals who have had prior ear surgery other than myringotomy, individuals with cochlear implants, individuals who require use of hearing aids.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hypertension; Turner Syndrome

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Veronica Gomez-Lobo, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2022
• First Posted: September 22, 2022
• Study Start: April 1, 2025
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)