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Master the board step 3

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<strong>Master</strong> <strong>the</strong> Boards: USMLE Step 3<br />

Maternal serum alpha<br />

fetoprotein (MS-AFP)<br />

increases with gestational<br />

age, and is expressed in<br />

multiples of <strong>the</strong> median<br />

(MoM).<br />

• > 2.2 MoM is considered<br />

elevated.<br />

• < 2.5 MoM is considered<br />

normal.<br />

Inhibin A is made by <strong>the</strong><br />

placenta during pregnancy<br />

and normally remains<br />

constant during 15th–18th<br />

week of pregnancy. The level<br />

of inhibin A is increased<br />

in <strong>the</strong> blood of mo<strong>the</strong>rs of<br />

fetuses with Down syndrome.<br />

Second Trimester<br />

A 23-year-old woman (G3 P1 Abortion 1) is seen at 17 weeks gestation. She recently<br />

underwent a triple marker screen with <strong>the</strong> maternal serum alpha fetoprotein (normal<br />

< 2.2 MoM). Her test showed an elevation in maternal serum alpha fetoprotein. On<br />

examination, her uterus is at <strong>the</strong> umbilicus. What is <strong>the</strong> next <strong>step</strong> in management?<br />

a. Amniocentesis<br />

b. Chorionic villus sampling<br />

c. Inhibin A<br />

d. Recommendation of termination of pregnancy<br />

e. Ultrasound<br />

Answer: E. The most common cause of an abnormal maternal serum alpha fetoprotein<br />

(MS-AFP) is gestational dating error. The first <strong>step</strong> in evaluating any pregnancy with an<br />

abnormal MS-AFP is to get an obstetric ultrasound to confirm <strong>the</strong> gestational date.<br />

Screening Test Diagnostic Significance Next Step in Management<br />

SECOND TRIMESTER OPTIONAL TESTS<br />

Triple Marker<br />

Screen<br />

Testing window<br />

is 15–20 weeks<br />

gestation.<br />

1. MS-AFP<br />

2. β-hCG<br />

3. Estriol<br />

4. Add Inhibin<br />

A in high-risk<br />

women (↑<br />

sens to 80%).<br />

• Never test MS-AFP alone:<br />

Only 20% sensitivity → ↑ to<br />

70% sensitivity with triple screen.<br />

• ↑ MS-AFP:<br />

Neural tube defect (NTD), ventral<br />

wall defect, twin pregnancy,<br />

placental bleeding, renal disease,<br />

sacrococcygeal teratoma<br />

• ↓ MS-AFP:<br />

– Trisomy 21 (Down syndrome)<br />

° ↓ MS-AFP<br />

° ↓ Estriol<br />

° ↑ β-hCG<br />

– Trisomy 18<br />

° ↓ MS-AFP<br />

° ↓ Estriol<br />

° ↓ β-hCG<br />

1) Abnormal MS-AFP:<br />

First <strong>step</strong> in management:<br />

• Perform ultrasound to confirm<br />

dating.<br />

• If dating error, repeat MS-AFP.<br />

• A normal repeat MS-AFP is<br />

reassuring.<br />

Note: Accurate gestational dating<br />

is needed for interpretation of<br />

results.<br />

2) Dates confirmed by ultrasound:<br />

Next <strong>step</strong> in management:<br />

For ↑ MS-AFP:<br />

a) Amniocentesis for amniotic<br />

fluid alpha fetoprotein (AF-AFP)<br />

level and acetylcholinesterase<br />

activity<br />

For ↓ MS-AFP:<br />

b) Amniocentesis for karyotyping<br />

Note: Elevated levels of amniotic<br />

fluid-acetylcholinesterase activity<br />

are specific to open NTD.<br />

AF-AFP = amniotic fluid alpha fetoprotein; MS-AFP = maternal serum alpha fetoprotein<br />

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