What is the most appropriate screening test for Down syndrome in a 40-year-old woman at 12 weeks of gestation?

First-Trimester Combined Screening is Most Appropriate at 12 Weeks

For this 40-year-old woman at 12 weeks gestation requesting Down syndrome screening, the most appropriate test is ultrasound for fetal nuchal translucency (NT) combined with first-trimester serum markers (PAPP-A and free beta-hCG or hCG), which together constitute first-trimester combined screening (Option D forms the foundation, but should be combined with serum markers). 1

Why First-Trimester Combined Screening at 12 Weeks

At 12 weeks gestation, first-trimester combined screening (maternal age + NT + PAPP-A + free beta-hCG) achieves detection rates of 83-86% for Down syndrome at a 5% false-positive rate. 1 This timing is optimal because:

• NT measurement is most accurate between 11-13 completed weeks gestation, and the patient is currently at the ideal window. 1
• Free beta-hCG performs better than intact hCG at 11-12 weeks (2-3% higher detection), making it the preferred serum marker at this gestational age. 1, 2
• For women 35 years and older (this patient is 40), the detection rate exceeds 80% when NT is combined with serum markers. 1

Why Other Options Are Less Appropriate

Triple Test (Option C) and Quadruple Test (Option A)

Both the triple test (AFP, hCG, uE3) and quadruple test (adds inhibin-A) are second-trimester screening tests performed between 15-20 weeks gestation, making them inappropriate for a patient currently at 12 weeks. 1

• The quadruple screen detects approximately 75% of Down syndrome cases in women younger than 35 years and over 80% in women 35 and older, but requires waiting until 15-20 weeks. 1
• Delaying screening until the second trimester means missing the opportunity for earlier diagnosis and the option of first-trimester diagnostic testing (CVS) if desired. 1

Nasal Bone Detection Alone (Option B)

While absent nasal bone between 11-13 weeks is a useful Down syndrome marker, it requires additional specialized training and should not be used as a standalone screening test. 1

• Nasal bone evaluation requires demonstration of proficiency beyond standard NT measurement and needs further validation for routine screening in the United States. 1
• It serves as an adjunct marker, not a primary screening modality. 1

NT Alone (Option D as stated)

While NT measurement is essential, using it without serum markers significantly reduces detection rates. 1

• NT measurement alone (with maternal age) has lower sensitivity than combined screening. 1
• The combination of NT with PAPP-A and free beta-hCG increases detection rates by approximately 20-25% compared to NT alone. 1

Optimal Screening Strategy for This Patient

The complete first-trimester combined screening protocol should include:

1. Ultrasound measurement of nuchal translucency between 11-13 completed weeks (patient is at 12 weeks—ideal timing). 1
2. Maternal serum PAPP-A measurement. 1
3. Maternal serum free beta-hCG (preferred at 12 weeks over intact hCG). 1, 2
4. Integration with maternal age (40 years—high-risk category). 1

Critical Considerations for Advanced Maternal Age

At age 40, this patient has significantly elevated baseline risk for Down syndrome, making accurate screening particularly important. 1

• Women 35 and older achieve detection rates exceeding 80% with combined first-trimester screening. 1
• Given her age, she should also be counseled about the option of diagnostic testing (CVS or amniocentesis) rather than screening alone. 1
• If first-trimester combined screening shows high risk, CVS can be offered immediately rather than waiting for second-trimester amniocentesis. 1

Important Pitfalls to Avoid

Do not delay screening to the second trimester when the patient presents at an optimal time for first-trimester testing. 1 Early screening provides:

• Earlier diagnosis if abnormalities are detected. 1
• More pregnancy management options. 1
• Reduced anxiety from earlier reassurance if results are normal. 1

Ensure NT measurements are performed by properly trained and credentialed sonographers, as technique significantly affects accuracy. 1