A Case of False Negative NIPT for Down Syndrome-Lessons Learned

Down syndrome or trisomy 21 is the most common cause of prenatal chromosome abnormalities with approximately 50% of all reported chromosome conditions. With the successful introduction of noninvasive prenatal testing (NIPT) for Down syndrome into routine prenatal care, it is important to understand the risks, benefits, and limitations in order to guide patients in making an informed decision. Herein, we describe the first published case report of a patient whose fetus tested “negative” for Trisomy 21 by NIPT but was diagnosed postnatally with trisomy 21. We present the importance of proper pretest and posttest genetic counseling to ensure prenatal patients are able to make informed decisions and are educated appropriately about NIPT. 1. Introduction It has been a little over two years since noninvasive prenatal testing (NIPT) was introduced as part of prenatal care to screen high-risk patients for fetal aneuploidy in the United States. Since then, the clinical use of NIPT has become increasingly common as it provides women with a more sensitive noninvasive screening option with detection rates reported as high as 99% for Down syndrome (DS) or Trisomy 21 [1]. Other clinical noninvasive screening modalities for DS include the first trimester screen with a detection rate of 75–80% and the maternal serum screen which has a detection rate of 80% [1]. NIPT evaluates cell-free DNA (cfDNA) that circulates in maternal blood and can be done as early as 9-week gestation [2]. While NIPT has shown to be both highly sensitive and highly specific across numerous studies [1, 3–11], the only diagnostic tests offered prenatally for DS or other aneuploidies are amniocentesis and chorionic villus (CVS) sampling. Several professional organizations, including the American College of Obstetrics and Gynecology (ACOG), the Society of Maternal Fetal Medicine (SMFM), and the National Society of Genetic Counselors (NSGC), have released position statements to help guide prenatal practices on the indications for use of NIPT [12, 13]. The overarching agreement among these organizations indicates that NIPT should only be offered to high-risk women as defined by (1) maternal age 35 years or older at delivery, (2) fetal ultrasound findings indicative of possible aneuploidy, (3) previous history of prior pregnancy with trisomy, (4) known familial robertsonian translocation, or a (5) previous positive prenatal screen [12, 13]. They also recommend NIPT testing only be given in context with pretest and posttest genetic counseling [12, 13]. Further, the American College of Medical Genetics