Genomic Sequencing for Pregnancy

Overseen By Nuriye Sahin Hodoglugil, DrPH

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Fetal anomaly, Decline testing, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

1000 Participants Needed

Trial Summary

What is the purpose of this trial?

This cohort study will examine the clinical utility of genomic sequencing (GS) in patients undergoing prenatal diagnostic procedures (chorionic villus sampling or amniocentesis) for routine indications other than a structural fetal anomaly.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Genomic Sequencing for Pregnancy?

Genomic sequencing, including whole genome and whole exome sequencing, has shown promise in accurately diagnosing diseases that are difficult to identify with traditional methods, and it has been particularly useful in neonatal intensive care settings, with a diagnostic success rate of about 40% and a significant impact on clinical management in over 20% of cases. ^{1 2 3 4 5}

Is genomic sequencing safe for use in pregnancy?

The research does not provide specific safety data for genomic sequencing in pregnancy, but it highlights ethical and practical considerations, such as informed consent and psychological impacts, which are important to address when using this technology. ^{4 6 7 8 9}

How is genomic sequencing for pregnancy different from other treatments for fetal anomalies?

Genomic sequencing for pregnancy is unique because it involves analyzing the entire genetic code of the fetus to identify potential anomalies, offering a comprehensive view of genetic variations. Unlike traditional methods, it can provide detailed insights into genetic disorders that might not be detectable through standard prenatal tests. ^{4 7 10 11 12}

Research Team

Mary Norton, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This clinical trial is for pregnant individuals undergoing routine prenatal diagnostic procedures like chorionic villus sampling or amniocentesis, but not because of a structural fetal anomaly. The study will include those who meet the specific conditions set by the researchers.

Inclusion Criteria

I plan to have prenatal tests (CVS or amniocentesis) with detailed chromosome analysis.

I have completed or am planning to complete expanded carrier screening.

Pregnant patients with a structurally normal fetus (singleton or multiple gestation)

Exclusion Criteria

I am pregnant and have chosen not to undergo prenatal diagnostic tests.

I am pregnant and my baby has been diagnosed with a health condition.

I am pregnant and chose not to have genetic screening tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genomic Sequencing

Participants undergo genomic sequencing to assess for additional disease risk, focusing on single gene disorders with a curated gene list.

Up to 2 months

1 visit (in-person) for sample collection

Follow-up

Participants are monitored for the reporting of genomic sequencing results and potential pregnancy management decisions.

4 weeks

Treatment Details

Interventions

• Genomic Sequencing

Trial Overview The trial is studying genomic sequencing (GS) to see how useful it is in understanding health information about fetuses that appear normal on anatomy scans during pregnancy.

Participant Groups

Group I: Genomic Sequencing Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Findings from Research

Human genomic sequencing can provide valuable insights for diagnosis, prognosis, and treatment across various medical fields, but its widespread use is limited by a lack of evidence showing improved patient outcomes in those without specific testing indications.

The paper reviews clinical outcome studies in genomic medicine, highlighting the challenges of generating robust evidence to support the integration of next-generation sequencing into standard patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building evidence and measuring clinical outcomes for genomic medicine. Peterson, JF., Roden, DM., Orlando, LA., et al.[2020]

Next-generation gene sequencing can sequence an individual's entire genome in under a week for $5000 to $10,000, making it a promising tool for diagnosing complex diseases that are hard to identify through traditional methods.

While there have been successful applications in diagnosing diseases and improving tumor management, significant challenges remain, including data interpretation, physician training, and the need for rigorous studies to validate its effectiveness in larger patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise and challenges of next-generation genome sequencing for clinical care. Johansen Taber, KA., Dickinson, BD., Wilson, M.[2022]

Genome-wide sequencing, including exome or whole genome sequencing, is recommended for patients suspected of having Mendelian diseases when conventional tests fail to identify the cause.

This approach is effective in pinpointing specific genetic causes of serious diseases, which can significantly enhance clinical care and patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controversy and debate on clinical genomics sequencing-paper 2: clinical genome-wide sequencing: don't throw out the baby with the bathwater! Adam, S., Friedman, JM.[2022]

Prenatal whole exome sequencing is a developing technology that could enhance the diagnostic options for clinicians managing pregnancies with identified fetal anomalies.

While it shows promise for future clinical use, it is not yet ready for routine practice, highlighting the need for further research and validation before widespread implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetal Exome Sequencing on the Horizon. Wou, K., DeBie, I., Carroll, J., et al.[2022]

Genomic sequencing, including exome and whole genome sequencing, has shown an average diagnostic yield of nearly 40% in neonatal intensive care units (NICUs), significantly aiding in identifying genetic conditions.

More than 20% of patients tested experienced immediate changes in clinical management due to genomic sequencing results, highlighting its importance as a standard of care in NICU settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exome and Whole Genome Sequencing in the Neonatal Intensive Care Unit. Muriello, M.[2022]

Exome sequencing (ES) and whole genome sequencing (WGS) are powerful tools for identifying harmful genetic variations, but they raise significant ethical concerns regarding informed consent, data sharing, and the handling of unexpected results.

Current practices in research and policy are not adequately addressing these ethical challenges, highlighting the need for new guidelines and resources to manage the implications of ES/WGS in genetics research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomics really gets personal: how exome and whole genome sequencing challenge the ethical framework of human genetics research. Tabor, HK., Berkman, BE., Hull, SC., et al.[2021]

Prenatal exome sequencing can provide valuable insights for diagnosing fetal anomalies, but healthcare providers must be aware of its complexities, including ethical considerations and the psychological impact on families.

Key factors to consider include the diagnostic yield, clinical utility, turnaround time, and costs associated with prenatal sequencing, which are essential for informed decision-making and counseling for expectant parents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prenatal exome and genome sequencing for fetal structural abnormalities. Vora, NL., Norton, ME.[2023]

Advancements in sequencing technologies have significantly reduced the cost and time required for whole-genome and whole-exome sequencing, making these methods more accessible for both research and clinical use.

The primary goal of newborn screening programs should be to identify gene variants that indicate a high risk for preventable or treatable conditions, allowing for early intervention and treatment during infancy or early childhood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes. Howard, HC., Knoppers, BM., Cornel, MC., et al.[2022]

Clinical gene sequencing is becoming more important and cost-effective, with a 25% increase in the number of genes linked to diseases over the past two years, which can help guide drug selection and predict health risks.

Current reporting methods for gene sequencing results are inadequate, often omitting crucial data and reference information, which can lead to data loss and complicate integration into electronic medical records. Standardized electronic reporting is needed to improve data preservation and accessibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of clinical gene sequencing data reporting and associated risks for information loss. Mitchell, DR., Mitchell, JA.[2009]

Clinical genome sequencing provides a more comprehensive diagnostic tool compared to traditional gene-panel or exome sequencing, offering valuable insights for timely diagnoses, especially in complex cases where previous tests have failed.

Despite its potential, the current use of genome sequencing is limited by the need for qualified clinicians to interpret the results and the technology's inability to detect all types of genetic variations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A primer to clinical genome sequencing. Priest, JR.[2019]

Whole genome sequencing (WGS) is becoming the preferred method for identifying genetic variations due to its comprehensive nature and decreasing costs, moving away from traditional microarray-based genotyping.

There are two main approaches to assembling genomic sequences from short reads: de novo assembly, which builds sequences by overlapping reads, and reference-based assembly, which maps reads to a known genome, each with its own advantages and challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole genome sequencing. Ng, PC., Kirkness, EF.[2022]

Whole exome sequencing can yield a substantial number of high-quality SNPs (single nucleotide polymorphisms) outside the targeted coding regions, with increases of 129% to 461% compared to SNPs within target regions across different sequencing platforms.

The study analyzed data from 22 subjects using Agilent SureSelect and 6 subjects using Illumina TrueSeq, revealing that these high-quality SNPs outside target regions are valuable and should be included in genetic epidemiology studies for a more comprehensive understanding of genetic variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exome sequencing generates high quality data in non-target regions. Guo, Y., Long, J., He, J., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Building evidence and measuring clinical outcomes for genomic medicine. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

The promise and challenges of next-generation genome sequencing for clinical care. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Controversy and debate on clinical genomics sequencing-paper 2: clinical genome-wide sequencing: don't throw out the baby with the bathwater! [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fetal Exome Sequencing on the Horizon. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Exome and Whole Genome Sequencing in the Neonatal Intensive Care Unit. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Genomics really gets personal: how exome and whole genome sequencing challenge the ethical framework of human genetics research. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Prenatal exome and genome sequencing for fetal structural abnormalities. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Status of clinical gene sequencing data reporting and associated risks for information loss. [2009]

10. United States pubmed.ncbi.nlm.nih.gov

A primer to clinical genome sequencing. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Whole genome sequencing. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Exome sequencing generates high quality data in non-target regions. [2021]