N/A
N=1,097
Prenatal Genetic Diagnosis by Genomic Sequencing
Fetal Structural Anomalies
Bottom Line
View on ClinicalTrials.gov: NCT03936101 ↗Enrolled (actual)
1,097
Serious AEs
0.0%
Results posted
Oct 2025
Primary outcome: Primary: Number of Participants Who Had Reportable Variants — 114; 22 Participants
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- Prenatal Genomic Sequencing (Diagnostic_test)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Columbia University
- Primary completion
- Mar 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Had Reportable Variants |
114; 22 | — |
| PRIMARY Healthcare Costs |
149985; 165192 | — |
| SECONDARY Gestational Age at Delivery |
37.4; 38.0 | — |
| SECONDARY Neonatal Outcomes |
222; 151; 24; 19; 89; 69 | — |
| SECONDARY Number of Deaths |
75; 37 | — |
| SECONDARY NICU Stay Duration |
6.0; 11.0 | — |
| SECONDARY Length in Centimeters |
73.7; 73.6 | — |
| SECONDARY Weight in Kilograms |
9.3; 9.6 | — |
| SECONDARY Score on Development by Ages and Stages Questionnaire (ASQ-3) |
45; 45; 40; 43; 50; 48 | — |
| SECONDARY Anxiety by Self-report Questionnaire |
2.0; 3.0; 2.0; 3.0; 2.0; 2.0 | — |
| SECONDARY Depression by Self-report Questionnaire |
4.0; 5.0; 4.0; 4.0; 3.0; 3.5 | — |
| SECONDARY Quality of Life by Self-report Questionnaire |
— | — |
| SECONDARY QALY, Measured in Cost Per Year |
— | — |
| SECONDARY Total Number of Identified Phenotypes Associated With Disease- Sequenced Group ONLY |
22 | — |
| SECONDARY Number of Participants With VUS - Sequenced Group ONLY |
7 | — |
| SECONDARY Number of Participants With Variants Classified as GUS - Sequenced Group ONLY |
— | — |
| SECONDARY Digital WES - Comparison of Coding and Non-coding Results - Sequenced Group ONLY |
— | — |
| SECONDARY Proband Only Versus Trio - Comparison of Results Between Trio and Proband Only - Sequenced Group ONLY |
— | — |
| SECONDARY Change in Management (Healthcare) as Determined by NICU Physician and Record Review - Sequenced Group ONLY |
72 | — |
| SECONDARY Parental Support Needs by Self-report Questionnaire - Sequenced Group ONLY |
56; 56 | — |
| SECONDARY Parental Understanding by Self-report Questionnaire - Sequenced Group ONLY |
0; 3; 1; 22; 5; 83 | — |
| SECONDARY Number of Participants Who Had a Change in the Sequencing Result - Sequenced Group ONLY |
7 | — |
| SECONDARY Turnaround Time - Sequenced Group ONLY |
11.5 | — |
Summary
This study is evaluating the impact of prenatal sequencing on the management of fetuses with ultrasound abnormalities. The hypothesis is that a significant subset of fetal abnormalities have a genetic cause that can be identified by sequencing and that prenatal knowledge of this information will improve prenatal care, reduce unnecessary diagnostic testing, reduce the cost of care, and improve the quality of life for both the child and the family.
Eligibility Criteria
Inclusion Criteria
Prenatal sequencing group
- Fetus identified by ultrasound and/or MRI with at least one of the following:
- One or more major structural anomalies (Appendix A)
- A nuchal translucency measurement of ≥ 3.5 mm
- A fetus less than 24 weeks 0 days gestation with normal anatomy and sonographically estimated fetal weight <5th %ile without maternal hypertension, type I diabetes, or other maternal disorders known to alter fetal growth.
- Negative prenatal CMA (or those with CMA findings not related to the ultrasound finding)
- Singleton or twin gestation
- Gestational age less than 36 weeks, 0 days to allow for availability of sequencing results before delivery
Unsequenced Group
- Fetus identified by ultrasound and/or MRI with at least one of the following:
- One or more major structural anomalies (Appendix A)
- A nuchal translucency measurement of ≥ 3.5 mm
- A fetus less than 24 weeks 0 days gestation with normal anatomy and sonographically estimated fetal weight <5th %ile without maternal hypertension, type I diabetes, or other maternal disorders known to alter fetal growth
- Negative prenatal or postnatal CMA (or those with CMA findings not related to the ultrasound finding)
- Declined prenatal sequencing
- Singleton gestation
Exclusion Criteria
Prenatal Sequencing Group
- Prenatal sequencing or planned prenatal sequencing performed outside of the study, including gene panels
- Maternal or paternal age less than 18 years old
- Proven infectious or teratogenic cause of fetal anomaly
- Planned termination of the pregnancy
- Unavailable blood or saliva samples from both biologic parents prior to sequencing
- Parental unwillingness to participate in 1 year postnatal follow-up
- Language barrier (non-English or Spanish speaking)
- Previous consent to the unsequenced prenatal group or enrollment in a previous pregnancy
Unsequenced Group
- Maternal or paternal age less than 18 years old
- Proven infectious or teratogenic cause of fetal anomaly
- Positive prenatal NIPT screening for trisomy 21,18 or 13. Positive 22q11.2 prenatal NIPT testing with consistent ultrasound findings is also an exclusion.
- Planned termination of the pregnancy
- Parental unwillingness to participate in 1 year postnatal follow-up
- Language barrier (non-English or Spanish speaking)
Data sourced from ClinicalTrials.gov (NCT03936101). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.