**Core Concept**
Trisomy-21, also known as Down syndrome, is a genetic disorder caused by the presence of an extra copy of chromosome 21. Diagnosing Trisomy-21 during pregnancy is crucial for proper management and planning. In the second trimester, various screening and diagnostic tests are available to detect this condition.

**Why the Correct Answer is Right**
The best way to diagnose Trisomy-21 during the second trimester is through amniocentesis. This invasive prenatal diagnostic test involves withdrawing a sample of amniotic fluid from the amniotic sac surrounding the fetus. The sample is then analyzed for the presence of chromosomal abnormalities, including Trisomy-21. The test is highly accurate, with a detection rate of over 99%. The presence of an extra copy of chromosome 21 can be confirmed through karyotyping or fluorescence in situ hybridization (FISH).

**Why Each Wrong Option is Incorrect**
* **Option A:** Non-stress test (NST) is a screening test used to monitor fetal well-being, but it is not a diagnostic test for Trisomy-21. It measures fetal heart rate in response to fetal movement, but it cannot detect chromosomal abnormalities.
* **Option B:** Maternal serum screening (MSS) involves measuring various substances in the mother's blood to assess the risk of Trisomy-21. While it can identify high-risk pregnancies, it is not a diagnostic test and requires confirmation through invasive testing.
* **Option D:** Ultrasound examination can detect some physical abnormalities associated with Trisomy-21, but it is not a definitive diagnostic test for the condition.

**Clinical Pearl / High-Yield Fact**
Amniocentesis is a crucial diagnostic test for Trisomy-21, but it carries a small risk of miscarriage. Therefore, it is usually offered to women who have a high risk of carrying a fetus with Trisomy-21, such as those over 35 years old or with a family history of the condition.

**Correct Answer: C. Amniocentesis.**