Finding Answers: Comprehensive Miscarriage,
Stillbirth & Neonatal Death Panel
Published on .
When families experience miscarriage, stillbirth, and neonatal deaths, there are often many difficult questions. Why did this happen? Will it happen again? Is there anything that could have prevented the outcome? At PreventionGenetics, we are dedicated to helping answer these questions.
Losses Are Common
Miscarriages occur in 15% of clinically recognized pregnancies. Although the majority of these losses occur early, 2-3% are in the second trimester (van den Berg et al. 2012; Hardy and Hardy 2015). Stillbirths occur in approximately 1 in 160 pregnancies in the United States (Wou et al. 2014). Neonatal death affects approximately 4 million babies annually worldwide (Jehan et al. 2009).
At least 50% of early miscarriages, 25% of stillbirths and 20% of neonatal deaths are due to abnormalities of the developing infant, most of which have a genetic basis. Genetic testing is important because many of these birth defects are difficult to recognize clinically. There are two major categories of genetic etiology for miscarriage, stillbirth, and neonatal death: chromosome abnormalities including triploidy, common aneuploidies (chromosomes 13, 18, 21, and X), other chromosomal imbalances (Wapner 2010), and single gene disorders, including, but not limited to, fetal akinesia syndrome, metabolic disorders, glycogen storage disorders, Noonan syndrome, and sudden cardiac death disorders (Wapner 2010; McPherson and Cold 2016; Sahoo et al. 2016).
The Comprehensive Miscarriage, Stillbirth, and Neonatal Death Panel includes Chromosomal Microarray (CMA-ISCA) followed by the 40 gene NextGen sequencing panel in cases with a normal microarray result. Chromosomal microarray (CMA-ISCA Test Code 2000, $990) and the Miscarriage, Stillbirth, and Neonatal Death NextGen Sequencing Panel (Test Code 4777, $1590) may also be ordered individually.
Chromosomal microarray (CMA) testing has been suggested as a first line test in both miscarriages and stillbirths because it does not require growing cells, as karyotyping does, and it will also detect submicroscopic imbalances (Reddy et al. 2012; American College of Obstetricians and Gynecologists 2013; Sahoo et al. 2016). If this is negative, the test would reflex to the 40 gene panel of single gene disorders.
The 40 gene NextGen sequencing panel was developed under collaboration between dual-certified molecular geneticist and cytogeneticist, Dr. Diane Allingham-Hawkins, and Dr. Elizabeth McPherson, experienced Medical Geneticist and Director of the Wisconsin Stillbirth Service Program, who has more than 30 years of experience evaluating stillbirths and neonatal deaths. This one-of-a kind panel encompasses several classes of genetic disorders that would be expected to increase the risk of miscarriage, stillbirth, or neonatal death. Disorders include Fetal Akinesia/Lethal Multiple Pterygium syndrome, Smith-Lemli-Opitz syndrome (SLOS), Noonan Spectrum Disorders, Peroxisomal Disorders, Glycogen Storage Disorders, and Long QT Syndrome.
Our Testing Strategy
As a gold sponsor of Seattle Children's Pediatric Laboratory Utilization Guidance Services (PLUGS®), we are proud to offer cost-effective testing strategies that align with utilization management best practices
If the CMA-ISCA tier of testing is positive, we charge only for that test ($990). If the full panel is performed and is negative ($2580), a reflex to PGxome may be ordered for an additional $990.
Chromosomal microarray (CMA-ISCA Test Code 2000, $990) and the Miscarriage, Stillbirth, and Neonatal Death NextGen Sequencing Panel (Test Code 4777, $1590) may also be ordered individually.
Our testing has been validated using whole blood (3-5 ml EDTA), umbilical cord blood (3-5 ml), fetal cell cultures (3-4 confluent T25 flasks from chorionic villus or amniocentesis cultures), DNA (5 ug at a concentration of at least 100 ng/ul), and fresh or frozen fetal tissue, including fetal placenta (2mm x 2mm x 2mm). As in all of our tests where there are risks for maternal cell contamination, we offer maternal cell contamination studies as a quality control measure for no additional cost.
Finding answers in tough situations is our expertise. However, at times, extensive testing may still leave unanswered questions. DNA Banking for Fetal Concerns is another service that we offer, which may provide hope for the future.
Help your patients find answers. Put Us To The Test.
Are you a patient looking for testing? Read our Patient Information
American College of Obstetricians and Gynecologists. 2013. ACOG committee opinion. Washington, DC: American College of Obstetricians and Gynecologists.
Hardy K., Hardy, P.J. 2015. Translational Pediatrics. 4: 189-200. PubMed ID: 26835373
Jehan I. et al. 2009. Bulletin of the World Health Organization. 87: 130-8. PubMed ID: 19274365
McPherson E., Cold C. 2016. American Journal of Medical Genetics. Part A. 170A: 52-9. PubMed ID: 26373818
Reddy U.M. et al. 2012. The New England Journal of Medicine. 367: 2185-93. PubMed ID: 23215556
Sahoo T. et al. 2016. Genetics in Medicine. 0: N/A. PubMed ID: 27337029
van den Berg M.M. et al. 2012. Biochimica Et Biophysica Acta. 1822: 1951-9. PubMed ID: 22796359
Wapner R.J. 2010. Clinical Obstetrics and Gynecology. 53: 628-34. PubMed ID: 20661047
Wou K. et al. 2014. BMJ Open. 4: e004635. PubMed ID: 24902725