Module 13 - Biomarkers in Adverse Pregnancy Outcomes

Question 1

What subunit of HCG is most commonly used to as a biomarker in pregnancy.

Answer 1

beta-HCG
(beta subunit)

Question 2

What is HCG a reflection of?

Answer 2

Trophoblastic Villous Activity

Question 3

How long does it take for bHCG to double?

Answer 3

1.5 days until 35 days.
2-2.5 days until 42 days.

Question 4

What proportion of US visible ectopic pregnancies are visible with bHCG <1,000?

Answer 4

80%

Question 5

What proportion of ectopic pregnancies and miscarriages mimic normal bHCG rise?

Answer 5

15% ectopic pregnancies.

8% miscarriages.

Question 6

What does progesterone levels reflect in pregnancy?

Answer 6

The interaction between trophoblastic tissue and corpus luteum.

(positive feedback from increase bHCG which increases progesterone produced by trophoblastic tissue).

Question 7

What is the sensitivity of predicting miscarriage in women with progesterone <20nmol/L (aka <6nm/ml)?

Answer 7

76% sensitive.

Question 8

Below what progesterone level has a strong PPV of progesterone?

Answer 8

<20nmol/L (aka <6nm/L).

Question 9

Above what progesterone level is there a ‘strong association’ of ongoing pregnancy?

Answer 9

> 60nmol/L (aka 19nm/L).

Question 10

Is progesterone level used clinically to predict chance of miscarriage? Why?

Answer 10

NO!
Too much natural variation with exogenous progesterone.

Question 11

What are markers of fallopian tube dysfunction?

Answer 11

1. Creatinine Kinase
   (enzyme released after muscle damage).
2. Smooth muscle heavy chain myosin.
3. Adrenomedullin (ADM) (peptide involved in cilliary beat activity).

Question 12

Why are fallopian tube dysfunction markers not used clinically?

Answer 12

Not enough supporting evidence.
CK has one study showing it is raised in ectopic pregnancy.

Question 13

What are markers of embryo or trophoblast dysfunction?

Answer 13

PAPP-A
PSG-I or SP-1 (preg specific beta glycoprotein 1)
hPL
Activin A
A Disintegrin
sFlt-1 (soluble vascular endothelial growth factor receptor)
PlGF
ADAM-12 (metalloprotease-12)

Question 14

Why are embryo or trophoblast dysfunction markers not used as an ectopic pregnancy biomarker?

Answer 14

Although evidence shows these are decreased in ectopic pregnancy, they are not produced until >7/40 therefore not clinically useful.

Question 15

What are the 2 biomarkers of corpus luteum function? (That are made in response to bHCG production)

Answer 15

Estradiol
Inhibin A

Question 16

Why are estradiol and Inhibin A not used in ectopic pregnancy diagnosis?

Answer 16

Because although generally thought to be reduced in ectopic pregnancies, there is conflicting data.

Question 17

What inflammation marker has a high PPV for ongoing pregnancy?

Answer 17

Ca125

Question 18

What other inflammation markers are raised in an ongoing pregnancy?

Answer 18

Ca125
IL2
IL6
IL8
TNF alpha