Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes

Schneuer, Francisco J.; Roberts, Christine L.; Ashton, Anthony W.; Guilbert, Cyrille; Tasevski, Vitomir; Morris, Jonathan M.; Nassar, Natasha

doi:10.1016/j.ajog.2013.11.012

Cited by 26 publications

(30 citation statements)

References 27 publications

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“…Subsequently, others authors confirmed the presence of an anti-angiogenic state in preeclampsia as well as in other pregnancy-related disorders [15,16]. Indeed, there is a growing body of evidence that anti-angiogenic mediators in maternal serum may serve as potential biomarkers for adverse pregnancy outcomes [17,18]. …”

Section: Discussionmentioning

confidence: 99%

Semaphorin 3F expression is reduced in pregnancy complicated by preeclampsia. An observational clinical study

et al. 2017

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Background and objectivePreeclampsia is a systemic disorder, affecting 2–10% of pregnancies, characterized by a deregulated pro- and anti-angiogenic balance. Semaphorin 3F is an angiogenesis inhibitor. We aimed to investigate whether semaphorin 3F expression is modulated in preeclampsia.Design, setting, participants, and measurementsWe performed two observational single center cohort studies between March 2013 and August 2014. In the first we enrolled 110 consecutive women, undergoing an elective cesarean section; in the second we included 150 consecutive women undergoing amniocentesis for routine clinical indications at 16–18 week of gestation. Semaphorin 3F concentration was evaluated in maternal peripheral blood, venous umbilical blood and amniotic fluid, along with its placenta protein expression at the time of delivery in the first study group and in the amniotic fluid at 16–18 weeks of gestation in the second study group.ResultsIn the first study 19 patients presented at delivery with preeclampsia. Semaphorin 3F placenta tissue expression was significantly reduced in preeclampsia. In addition, semaphorin 3F level at delivery was significantly lower in serum, amniotic fluid and venous umbilical blood of preeclamptic patients compared with normal pregnant women. In the prospective cohort study 14 women developed preeclampsia. In this setting, semaphorin 3F amniotic level at 16–18 weeks of gestation was reduced in women who subsequently developed preeclampsia compared to women with a normal pregnancy. ROC curve analysis showed that semaphorin 3F amniotic levels could identify women at higher risk of preeclampsia.ConclusionsSemaphorin 3F might represent a predictive biomarker of preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Semaphorin 3F expression is reduced in pregnancy complicated by preeclampsia. An observational clinical study

et al. 2017

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“…These associations may suggest the role of angiogenic/anti-angiogenic factors in the pathogenesis of adverse pregnancy outcomes, however, their value in screening of women at-risk of these conditions may be not appropriate in a clinical setting. In a recent study, we found that despite a positive association between elevated first trimester Ang-1/Ang-2 ratio levels with SGA, preeclampsia, preterm birth and miscarriage in a large cohort of women 9 , the overall predictive accuracy was poor. Strengths of the study were the evaluation of a large sample from a population-based cohort of pregnant women attending first trimester screening.…”

Section: Discussionmentioning

confidence: 99%

“…Ang-1 and Ang-2 concentrations were available for 1,058 women and were obtained from data from a previous study 9 . 21 and categorized into quintiles.…”

Section: Data Sourcesmentioning

confidence: 99%

“…We have previously reported an association between low first trimester serum levels of Ang-2 with the subsequent development of preeclampsia, small for gestational age infant, preterm birth and miscarriage 9 . We hypothesise that the Ang-2/Tie-2 binding mechanism would be altered in compromised pregnancies and therefore be expressed in abnormal first trimester sTie-2 serum levels.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of first trimester serum soluble endothelial cell-specific tyrosine kinase receptor in normal and affected pregnancies

Schneuer

Nassar

Guilbert

et al. 2014

The Journal of Maternal-Fetal & Neonatal Medicine

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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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“…Biomarkers and biophysical tests may improve the accuracy of the model beyond using maternal characteristics alone. Published studies show only a limited contribution of these factors to improved discriminative performance, however . Moreover, most of these more complex predictors are relatively expensive, not readily available in general antenatal settings, and are possibly inconvenient for pregnant women .…”

Section: Introductionmentioning

confidence: 99%

External validation and clinical usefulness of first‐trimester prediction models for small‐ and large‐for‐gestational‐age infants: a prospective cohort study

Meertens

Smits

Kuijk

et al. 2019

BJOG

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Objective To assess the external validity of all published first‐trimester prediction models based on routinely collected maternal predictors for the risk of small‐ and large‐for‐gestational‐age ( SGA and LGA ) infants. Furthermore, the clinical potential of the best‐performing models was evaluated. Design Multicentre prospective cohort. Setting Thirty‐six midwifery practices and six hospitals (in the Netherlands). Population Pregnant women were recruited at <16 weeks of gestation between 1 July 2013 and 31 December 2015. Methods Prediction models were systematically selected from the literature. Information on predictors was obtained by a web‐based questionnaire. Birthweight centiles were corrected for gestational age, parity, fetal sex, and ethnicity. Main outcome measures Predictive performance was assessed by means of discrimination (C‐statistic) and calibration. Results The validation cohort consisted of 2582 pregnant women. The outcomes of SGA <10th percentile and LGA >90th percentile occurred in 203 and 224 women, respectively. The C‐statistics of the included models ranged from 0.52 to 0.64 for SGA ( n = 6), and from 0.60 to 0.69 for LGA ( n = 6). All models yielded higher C‐statistics for more severe cases of SGA (<5th percentile) and LGA (>95th percentile). Initial calibration showed poor‐to‐moderate agreement between the predicted probabilities and the observed outcomes, but this improved substantially after recalibration. Conclusion The clinical relevance of the models is limited because of their moderate predictive performance, and because the definitions of SGA and LGA do not exclude constitutionally small or large infants. As most clinically relevant fetal growth deviations are related to ‘vascular’ or ‘metabolic’ factors, models predicting hypertensive disorders and gestational diabetes are likely to be more specific. Tweetable abstract The clinical relevance of prediction models for the risk of small‐ and large‐for‐gestational‐age is limited.

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Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes

Cited by 26 publications

References 27 publications

Semaphorin 3F expression is reduced in pregnancy complicated by preeclampsia. An observational clinical study

Semaphorin 3F expression is reduced in pregnancy complicated by preeclampsia. An observational clinical study

Evaluation of first trimester serum soluble endothelial cell-specific tyrosine kinase receptor in normal and affected pregnancies

External validation and clinical usefulness of first‐trimester prediction models for small‐ and large‐for‐gestational‐age infants: a prospective cohort study

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