Biomarkers in Early Pregnancy Max Brinsmead MB BS PhD January 2019

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

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)

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

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

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

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

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

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

Predicting Gestational Diabetes Elevated fasting blood glucose in the first trimester has sensitivity of 55 – 75% and specificity of 52 - 75% 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

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

Any Questions or Comments? Please leave a Note on the Welcome Page to this Website