1. Biomarkers in Early Pregnancy
Max Brinsmead MB BS PhD
January 2019

2. Resource for this Presentation:
RCOG Scientific Impact Paper
November 2018
First Trimester Biomarkers in the Prediction of Later Pregnancy Complications
Kane,da Silva Costa & Brennecke, Melbourne
December 2014

3. What is a Biomarker?
Any substance, structure or process that can be measured in the body or its products and used to influence or predict the incidence and outcome or the course of a disease
Common biomarkers in early pregnancy include beta-HCG, Progesterone and ultrasound (particularly transvaginal ultrasound or TVS)

4. Predicting What? Ectopic pregnancy
Pregnancy outcome – progressive or miscarriage
Molar pregnancy, partial mole or missed miscarriage
Complications of later pregnancy including pre eclampsia, growth retardation & premature delivery

5. Beta HCG Single measures not much use
especially if it is a multiple pregnancy
78% ectopics have ß-HCG below 1000 when visible by ultrasound
Doubles every 1.5 days to Day 35 and every 2 days until Day 42
Failure to rise is 66% predictive of ectopic and 90% predictive of miscarriage
But up to 20% of ectopics and 8% of miscarriages will have normal pattern rise

6. Progesterone
Single measure >60 nmol/L highly predictive of successful pregnancy
Single measure of <20 nmol/L identifies 76% of non viable pregnancies
Especially with bleeding and or pain and inconclusive ultrasound
Of no use if exogenous progesterone is being used
Injected, oral or vaginal as in luteal support after IVF

7. Other Biomarkers for Pregnancy Prognosis
Cell-free microRNAs – promising
Higher maternal CA125 – “highly predictive of ongoing pregnancy”
Lower Leukemia Inhibitory Factor (LIF) & higher Vascular Endothelial Growth Factor (VEGF) – promising
PAPP-A, SP-1, HPL and Placental Growth Factor (PIGF) all lower in ectopic pregnancy but only appear after 7 weeks therefore of limited value

8. Predicting Pre eclampsia
A combination of tests can predict pre eclampsia with 93% sensitivity and 5% false positive rate
Uses mean arterial BP, uterine artery Doppler, PAPP-A and PIGF (Placental growth factor)
Aspirin and other therapy trials on this basis
Other biomarkers include Inhibin A, Activin A, EGF and their inhibitors

9. Predicting Fetal Growth Restriction
One large study identified 73% of IUGR using first trimester US nuchal translucency (NT), ß-HCG, PAPP-A, uterine artery Doppler, PIGF, Placental protein 13, and two other markers, 11% false positive rate
Ultrasound measures of placental volume also have a role

10. Predicting Gestational Diabetes
Elevated fasting blood glucose in the first trimester has sensitivity of 55 – 75% and specificity of %
Other markers of use include sex hormone binding globulin (SHBG), highly sensitive C-reactive protein and adiponectin
When used in combination can predict about 75% with 20% false positive rate

11. Predicting Preterm Birth
Meta-analyses of 116 biomarkers studied over the last four decades and 30 novel biomarkers investigated over the last ten years have concluded that none perform sufficiently in predicting preterm birth to be clinically useful.
One study of ultrasound-measured short cervix predicted 55% of deliveries <34 weeks
Vaginal measures of Fetal Fibronectin in later pregnancy up to 50% predictive when positive and up to 100% predictive when negativee
A quantified rapid test demonstrates better results

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