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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the usefulness of genomic sequencing (a detailed look at genes) for pregnant patients undergoing routine prenatal tests like chorionic villus sampling or amniocentesis. The researchers aim to determine if this genetic information offers more insights during pregnancy, especially when ultrasounds show a normal baby. Pregnant individuals with a structurally normal fetus planning these specific prenatal tests might be suitable candidates. This approach could provide early insights into the baby's health. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance prenatal care.

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 prior data suggests that genomic sequencing is safe for prenatal diagnostic procedures?

Research has shown that genomic sequencing (GS) is generally safe for prenatal testing. This method aids in early understanding of genetic disorders by examining many genes, helping doctors make informed decisions during pregnancy.

No major safety concerns have been reported with genomic sequencing itself. The method is safe for the baby because it uses samples already collected for other tests. Experts believe the benefits of early detection of potential genetic issues outweigh the risks.

Overall, the process is well-tolerated, and earlier studies have not consistently reported serious problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Genomic sequencing for pregnancy is unique because it allows for an incredibly detailed look at the genetic makeup of both the mother and the developing fetus. Unlike traditional methods, such as ultrasound or standard blood tests, genomic sequencing can identify a wide range of genetic conditions early on with remarkable accuracy. Researchers are excited because this approach could lead to earlier interventions or better-informed decisions during pregnancy, potentially improving outcomes for both the mother and the baby. This method represents a significant leap forward in prenatal care by providing comprehensive genetic insights that current standard practices simply can't match.

What evidence suggests that genomic sequencing is effective for prenatal diagnostics?

Research has shown that genetic testing methods, such as whole exome sequencing (WES), effectively diagnose genetic conditions. Previous studies found that WES identified genetic issues in up to 30% of patients with suspected genetic problems, uncovering abnormalities in nearly one-third of cases that other methods couldn't diagnose. Additionally, whole genome sequencing (WGS) offers a detailed view of most genes in the human body, providing a broad perspective on genetic health. In this trial, participants will undergo genomic sequencing, which can be particularly beneficial for expectant parents by identifying potential genetic conditions early in pregnancy. ^{1 6 7 8 9}

Who Is on the Research Team?

Mary Norton, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5745303/

Promises, pitfalls and practicalities of prenatal whole exome ... In postnatal testing, WES studies have demonstrated a diagnostic yield of 25% to 30% in patients suspected to have a genetic condition undiagnosed using ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2814303

Cost-Effectiveness of Whole-Genome vs Whole-Exome ... Our data suggest that WGS is cost-effective for diagnosing infants with potential genetic disorders at a WTP threshold of €30 000 to €50 000 (US ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03482141

Clinical Utility of Prenatal Whole Exome Sequencing Whole exome sequencing (WES) and whole genome sequencing (WGS) have the advantage of enabling parallel interrogation of most of the genes in the human genome.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1521693424000932

Genome sequencing in the prenatal diagnosis of structural ... This chapter aims to illustrate the detection scope and feasibility of various NGS-based methods that are currently used in prenatal diagnosis.

5. journals.lww.com journals.lww.com/obgynsurvey/fulltext/2025/09000/exome_sequencing_in_every_pregnancy__results_of.8.aspx

Exome Sequencing in Every Pregnancy? Results of Trio ... The authors conclude that the diagnostic yield of 2.7% justifies prenatal diagnosis with exome sequencing in all pregnancies, with the caveat and discussion of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03482141

Clinical Utility of Prenatal Whole Exome Sequencing Whole exome sequencing (WES) and whole genome sequencing (WGS) have the advantage of enabling parallel interrogation of most of the genes in the human genome.

7. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.6890?af=R

The Expanding Role of Gene Sequencing in Shaping Fetal ... Next generation sequencing enables early genetic testing, playing a pivotal role in prenatal decision-making by supporting risk stratification, ...

8. clinicalcases.eu clinicalcases.eu/index.php/acc/article/download/1175/352/2914

The evolution of prenatal Whole Exome Sequencing The emergence of Whole Exome Sequencing (WES) has impacted prenatal genetic diagnostics in a transformative way, enabling clinicians to detect ...

9. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2016/12/microarrays-and-next-generation-sequencing-technology-the-use-of-advanced-genetic-diagnostic-tools-in-obstetrics-and-gynecology

Microarrays and Next-Generation Sequencing Technology ... This Committee Opinion reviews and makes recommendations regarding the application of two of the newer genetic technologies in the prenatal setting.