Low 25(OH)D serum concentrations in the first trimester of pregnancy are not associated with adverse pregnancy outcomes and do not predict complications any better than routinely assessed clinical and maternal risk-factor information.
Word count:Abstract: 250 Text: 3,183 2 Condensation: Ang-2 and the Ang-1/Ang2 ratio is associated with several adverse pregnancy outcomes but do not predict complications any better than maternal risk factors Short title: Ang-1 and Ang-2 as biomarkers of adverse pregnancy outcomes 3
ABSTRACTObjective: To assess Ang-1, 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.Study Design: This cohort study measured serum Ang-1 and Ang-2 levels in 4,785 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 socio-economic 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 (<10 th centile) and high Ang-1/Ang-2 ratio (>90 th centile) had increased risk of developing most adverse pregnancy outcomes.Compared to 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 ROC curve (AUC) =0.70; maternal risk factors AUC =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.
Maternal first trimester serum concentrations of sFlt-1 and PlGF do not predict hypertensive disorders in pregnancy any better than routinely collected clinical and maternal risk factor information. Screening for sFlt-1 and PlGF levels in early pregnancy would not identify those pregnancies at-risk.
Short title: sTie-2 on pregnancy outcomesKey words: sTie-2 receptor, first trimester, adverse pregnancy outcomes, serum levels, predictive accuracy 2 ABSTRACT Aims: To assess soluble endothelial cell-specific tyrosine kinase receptor (sTie-2) levels in the first trimester of pregnancy and its association with adverse pregnancy outcomes; and examine the predictive accuracy.Study Design: In this nested case-control study, serum sTie-2 levels were measured in 2,616 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 sTie-2 with subsequent adverse pregnancy outcomes.Results: Median (interquartile range) sTie-2 for the total population was 19.6 ng/ml (13.6-26.4). Maternal age, weight, and smoking status significantly affected sTie-2 levels. There was no difference in serum sTie-2 between unaffected and women with adverse pregnancy outcomes. After adjusting maternal and clinical risk factors, low sTie-2 (<25 th centile) was associated with preeclampsia (Adjusted odds ratio: 1.61; 95%CI: 1.01-2.57), however, the accuracy of sTie-2 in predicting preeclampsia was not different from chance (AUC=0.54; P=0.08) and does not add valuable predictive information to maternal and clinical risk factors.
Conclusions:Our findings suggest that low sTie-2 levels are associated with preeclampsia, however, it does not add valuable information to clinical and maternal risk factor information in predicting preeclampsia or any other adverse pregnancy outcomes.3
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