A 37-year-old woman presents for prenatal counseling at 18 weeks gestation. The patient tells you that her sister recently had a child with Down's syndrome, and the patient would like prenatal screening for Down's in her current pregnancy. Which of the following prenatal screening tests and results would raise concern for Down's syndrome?

Decreased AFP, increased HCG, decreased unconjugated estriol

Increased AFP, normal HCG, normal unconjugated estriol

Decreased AFP, decreased HCG, decreased unconjugated estriol

Normal AFP, increased HCG, decreased unconjugated estriol

Normal AFP, decreased HCG, decreased unconjugated estriol

A 36-year-old G3P2002 presents to her obstetrician’s office for her first prenatal visit at ten weeks and two days gestation. She notes that she has felt nauseous the last several mornings and has been especially tired for a few weeks. Otherwise, she feels well. The patient has had two uncomplicated spontaneous vaginal deliveries at full term with her last child born six years ago. She is concerned about the risk of Down syndrome in this fetus, as her sister gave birth to an affected child at age 43. The patient has a history of generalized anxiety disorder, atopic dermatitis, and she is currently on escitalopram. At this visit, this patient’s temperature is 98.6°F (37.0°C), pulse is 70/min, blood pressure is 121/67 mmHg, and respirations are 13/min. The patient appears anxious, but overall comfortable, and cardiopulmonary and abdominal exams are unremarkable. Pelvic exam reveals normal female external genitalia, a closed and slightly soft cervix, a ten-week-sized uterus, and no adnexal masses. Which of the following is the best next step for definitively determining whether this patient’s fetus has Down syndrome?

Genetic testing of patient’s sister

A 26-year-old G1P0 mother is in the delivery room in labor. Her unborn fetus is known to have a patent urachus. Which of the following abnormalities would you expect to observe in the infant?

Meconium discharge from umbilicus

A 45-day-old male infant is brought to a pediatrician by his parents with concerns of poor feeding and excessive perspiration for one week. On physical examination, his temperature is 37.7°C (99.8°F), pulse rate is 190/min, and respiratory rate is 70/min. Mild cyanosis is present over the lips, and over the nail beds. Oxygen is provided and his oxygen saturation is carefully monitored. The pediatrician orders a bedside echocardiogram of the infant. It reveals a single arterial trunk arising from 2 normally formed ventricles. The arterial trunk is separated from the ventricles by a single semilunar valve. There is a defect in the interventricular septum, and the arterial trunk overrides the defect. Which of the following congenital heart diseases can also present with similar clinical features?

Transposition of the great arteries with ventricular septal defect and pulmonary stenosis

Infracardiac total anomalous pulmonary venous return

Pulmonary atresia with intact ventricular septum

Double-inlet ventricle with unobstructed pulmonary flow

A 25-year-old woman, gravida 2, para 1, comes to the physician for her initial prenatal visit at 18 weeks’ gestation. She is a recent immigrant from Thailand. Her history is significant for anemia since childhood that has not required any treatment. Her mother and husband have anemia, as well. She has no history of serious illness and takes no medications. Her vital signs are within normal limits. Fundal height measures at 22 weeks. Ultrasound shows polyhydramnios and pleural and peritoneal effusion in the fetus with fetal subcutaneous edema. Which of the following is the most likely clinical course for this fetus?

Normal development with regular blood transfusion

Prenatal diagnosis of congenital defects for USMLE Step 1: High-Yield Pediatrics Lessons

Prenatal Screening - The First Look

First Trimester (11-13+6 wks): Combined test is standard.
- Biochemical: ↑ free β-hCG, ↓ PAPP-A.
- USG: ↑ Nuchal Translucency (NT).
Second Trimester (15-20 wks): Quadruple test.
- Markers: ↓ AFP, ↑ β-hCG, ↓ uE3, ↑ Inhibin A.
NIPS/NIPT: Non-invasive prenatal screening/testing. Highest detection rate for aneuploidies.

⭐ In Down Syndrome, all markers in the second-trimester screen are down except for hCG and Inhibin A, which are high.

Fetal Nuchal Translucency (NT) Ultrasound Measurement

1st Trimester Screening - The Early Birds

When: 11-14 weeks gestation (or CRL 45-84 mm).
What: A combined screening test for aneuploidies (Trisomy 21, 18, 13).
Components:
- Biochemical Markers (Double Marker Test):
  - ↓ PAPP-A (Pregnancy-Associated Plasma Protein-A)
  - ↑ Free β-hCG (human chorionic gonadotropin)
- Sonographic Markers (NT Scan):
  - ↑ Nuchal Translucency (NT)
  - Absent/Hypoplastic Nasal Bone

Fetal Ultrasound: Nuchal Translucency Measurement

⭐ The combined test boasts a detection rate of ~85% for Down Syndrome. It is a screening test; positive results require diagnostic confirmation (e.g., CVS or amniocentesis).

2nd Trimester Screening - The Mid-Game Scan

Timing: 15-20 weeks (ideal: 16-18 weeks).
Tests: Ultrasound (for anomalies) + Maternal serum screening.
Quadruple Test: Measures 4 markers:
- Alpha-fetoprotein (AFP)
- Human chorionic gonadotropin (hCG)
- Unconjugated estriol (uE3)
- Inhibin A

Fetal ultrasound images for prenatal anomaly detection

⭐ The Quadruple test has a detection rate of approximately 80% for Down syndrome.

Invasive Diagnostic Tests - The Decisive Divers

Definitive diagnosis for chromosomal/genetic disorders. Involves sampling fetal tissue/fluid, each with specific timing and risks.

Test	Gestational Age (GA)	Risk of Fetal Loss	Key Points
Chorionic Villus Sampling (CVS)	10-13 wks	~1%	Earliest test. Cannot detect NTDs.
Amniocentesis	15-20 wks	~0.5%	Can detect NTDs (↑AFP).
Cordocentesis (PUBS)	>18 wks	1-2%	Rapid karyotype; fetal therapy.

NIPT & Beyond - The DNA Detective

Non-Invasive Prenatal Testing (NIPT): Analyzes cell-free fetal DNA (cffDNA) from maternal plasma.
- Performed from 10 weeks gestation onwards.
- Screens for common aneuploidies (Trisomy 21, 18, 13) & sex chromosome abnormalities.
- High detection rate for Down syndrome (>99%).
Confirmatory Tests: NIPT is a screening tool; positive results require confirmation via Chorionic Villus Sampling (CVS) or Amniocentesis.

⭐ Fetal Fraction: The proportion of cffDNA in maternal blood. A level <4% is a major cause of NIPT failure or false-negative results.

High‑Yield Points - ⚡ Biggest Takeaways

Nuchal Translucency (NT) is the most important first-trimester ultrasound marker for Down syndrome.

The double marker test (PAPP-A, β-hCG) is the key first-trimester biochemical screen.

The quadruple screen (AFP, hCG, estriol, inhibin A) is the standard second-trimester biochemical test.

Amniocentesis (15-20 weeks) and Chorionic Villus Sampling (CVS) (10-13 weeks) are the primary invasive diagnostic tests.

Cell-free fetal DNA (cffDNA) is the most sensitive non-invasive screening test for aneuploidy.

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