Missed Down Syndrome Cases after First Trimester False-Negative Screening-Lessons to be Learned

Area of Science:

• Prenatal Diagnosis
• Genetics
• Obstetrics

Background:

• First-trimester screening for Down syndrome (DS) traditionally relies on ultrasound markers, biochemical levels, and risk calculation software.
• Variability in operator skill and adherence to standardized protocols can impact the accuracy of prenatal DS screening.
• Previous studies highlight the need for improved methodologies in prenatal screening to reduce false-negative diagnoses.

Purpose of the Study:

• To analyze the incidence of misdiagnosed and false-negative Down syndrome (DS) cases in Romania between 2010-2015.
• To identify areas for improvement in first-trimester prenatal DS screening protocols.
• To emphasize the need for standardized measurements, accurate dating, and high-quality laboratory performance in prenatal screening.

Main Methods:

• Descriptive analysis of a database search for Down syndrome (DS) cases from 2010-2015.
• Utilized data from two prenatal DS risk calculation software programs: Astraia and Prisca.
• Evaluated first-trimester screening using nuchal translucency, nasal bone, ductus venosus flow, tricuspid flow, free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein-A.

Main Results:

• Seven Down syndrome (DS) cases were identified with initially low-risk results.
• Astraia software missed three DS cases, while Prisca software missed four DS cases.
• One case of atrio-ventricular canal defect was also missed during prenatal diagnosis.

Conclusions:

• Current prenatal DS screening practices in Romania are susceptible to false-negative results due to operator dependency and lack of standardization.
• Standardized protocols, professional guidelines, and audit controls are essential for enhancing the accuracy of first and second-trimester combined screening.
• Improving the application of prenatal DS screening programs is vital for accurate trisomy 21 risk assessment.