**Core Concept**
The question is testing the understanding of the optimal diagnostic approach for Down syndrome (Trisomy 21) during early pregnancy, specifically at 15 weeks of gestation. This involves the use of non-invasive prenatal testing (NIPT) and/or screening tests to identify individuals at increased risk.

**Why the Correct Answer is Right**
Non-invasive prenatal testing (NIPT) using cell-free DNA (cfDNA) from maternal blood is the preferred method for screening and diagnosing Down syndrome at 15 weeks of gestation. This is particularly relevant for women with a previous history of delivering a Down syndrome baby, as they are at increased risk. The cfDNA test measures the levels of chromosome 21 DNA in the maternal blood, which are elevated in cases of Down syndrome. This allows for an accurate risk assessment and, in some cases, a definitive diagnosis.

**Why Each Wrong Option is Incorrect**
**Option A:** Ultrasound markers such as nuchal translucency (NT) are used for screening, but they are not the investigation of choice for diagnosing Down syndrome at 15 weeks. While NT can indicate an increased risk, it does not provide a definitive diagnosis.
**Option B:** Amniocentesis is an invasive diagnostic test that involves withdrawing amniotic fluid from the uterus. While it can provide a definitive diagnosis of Down syndrome, it carries a risk of miscarriage and is not typically performed at 15 weeks.
**Option C:** Chorionic villus sampling (CVS) is another invasive diagnostic test that involves removing a small sample of placental tissue. Like amniocentesis, it can provide a definitive diagnosis but carries a risk of miscarriage and is not typically performed at 15 weeks.

**Clinical Pearl / High-Yield Fact**
When counseling patients with a history of delivering a Down syndrome baby, it is essential to discuss the benefits and risks of NIPT, including its accuracy and the potential for false positives or false negatives. This allows patients to make informed decisions about their prenatal care.

**Correct Answer: B. Amniocentesis is an invasive diagnostic test that involves withdrawing amniotic fluid from the uterus. While it can provide a definitive diagnosis of Down syndrome, it carries a risk of miscarriage and is not typically performed at 15 weeks.