Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes.
OBJECTIVE
To assess angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the Ang-1/Ang-2 ratio levels in the first trimester of pregnancy, their association with adverse pregnancy outcomes, and their predictive accuracy.


METHODS
This cohort study measured serum Ang-1 and Ang-2 levels in 4785 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum biomarkers with subsequent adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, miscarriage >10 weeks, and stillbirth).


RESULTS
Median (interquartile range) levels for Ang-1, Ang-2, and the Ang-1/Ang-2 ratio for the total population were 19.6 ng/mL (13.6-26.4), 15.5 ng/mL (10.3-22.7), and 1.21 (0.83-1.73), respectively. Maternal age, weight, country of birth, and socioeconomic status significantly affected Ang-1, Ang-2, and the Ang-1/Ang-2 ratio levels. After adjusting for maternal and clinical risk factors, women with low Ang-2 levels (<10th percentile) and high Ang-1/Ang-2 ratio (>90th percentile) had increased risk of developing most adverse pregnancy outcomes. Compared with the Ang-1/Ang-2 ratio alone, maternal and clinical risk factors had better predictive accuracy for most adverse pregnancy outcomes. The exception was miscarriage (Ang-1/Ang-2 ratio area under receiver operating characteristic curve = 0.70; maternal risk factors = 0.58). Overall, adding the Ang-1/Ang-2 ratio to maternal risk factors did not improve the ability of the models to predict adverse pregnancy outcomes.


CONCLUSIONS
Our findings suggest that the Ang-1/Ang-2 ratio in first trimester is associated with most adverse pregnancy outcomes, but do not predict outcomes any better than clinical and maternal risk factor information.
Clinical and Population Perinatal Health Research, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia. Electronic address: francisco.schneuer@sydney.edu.au.
Francisco J
FJ
Schneuer
Clinical and Population Perinatal Health Research, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Christine L
CL
Roberts
Clinical and Population Perinatal Health Research, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Anthony W
AW
Ashton
Clinical and Population Perinatal Health Research, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Cyrille
C
Guilbert
Fetal Maternal Medicine (PaLMs), Royal North Shore Hospital, St Leonards, NSW, Australia.
Vitomir
V
Tasevski
Clinical and Population Perinatal Health Research, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Jonathan M
JM
Morris
Clinical and Population Perinatal Health Research, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
Natasha
N
Nassar
D000022:Abortion, Spontaneous / Q000097:blood; D000328:Adult; D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D015331:Cohort Studies; D005006:Ethnicity; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008423:Maternal Age; D015999:Multivariate Analysis; D011225:Pre-Eclampsia / Q000097:blood; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First / Q000097:blood*; D047928:Premature Birth / Q000097:blood; D012372:ROC Curve; D012923:Social Class
C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers
Ang-1; Ang-2; adverse pregnancy outcomes; angiopoietins; first trimester; serum levels