Longitudinal circulating placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1) concentrations during pregnancy in Asian women: a prospective cohort study

Ng, Qiu Ju; Han, Jonathan Youxiang; Saffari, Seyed Ehsan; Yeo, G. S. H.; Chern, Bernard; Tan, Kok Hian

doi:10.1136/bmjopen-2018-028321

Cited by 11 publications

(6 citation statements)

References 20 publications

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“…Concentrations of sFlt-1 remain fairly constant in the maternal circulation until 33–36 weeks’ gestation and are known to increase approximately five weeks before the onset of PE. 15–17 This expected rise was not apparent within our study at either time point; however, this finding may be attributed to the earlier gestation at which sFlt-1 was sampled. Additional sampling of sFlt-1 at a later gestation could provide additional information.…”

Section: Discussioncontrasting

confidence: 54%

The role of biomarkers in predicting pre-eclampsia in high-risk women

et al. 2019

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Background There are limited data on performance of biomarkers to predict pre-eclampsia (PE) in high-risk women. This study investigated the ability of FABP4, PAPP-A, PlGF, sFlt-1 and sEng to predict PE in a high-risk group. Methods Non-fasting samples were analysed at 11 + 0–13 + 6 (V1) and 19 + 0–21 + 6 weeks (V2) ( n = 195). Logistic regression models were determined. Area under (AUC) the receiver operating characteristic (ROC) curve analysis was performed. The added value of biomarkers to clinical characteristics for PE prediction was quantified using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices. Results Prevalence of PE was 12%. Lower concentrations of sFlt-1:PlGF (V1) and PlGF and PlGF:sEng (V2) were seen in women who developed PE. Controlling for baseline characteristics (V1), a doubling of sFlt-1 (pg/mL) (median 896.0, IQR 725.5–1097.0) and sFlt-1:PlGF (median 21.2, IQR 14.7–32.3) was associated with reduction in odds of PE (OR 0.20, 95% CI 0.06–0.65, P = 0.007 and OR 0.48, 95% CI 0.25–0.92, P = 0.04). Addition of sFlt-1 and sFlt-1:PlGF to baseline characteristics non-significantly improved AUC (0.74) (AUC 0.77, P = 0.40 and 0.76, P = 0.39). NRI and IDI analyses confirmed added clinical utility of sFlt-1 (NRI = 0.539, P = 0.01 and IDI = 0.052, P = 0.03). In V2, doubling of PlGF:sEng (median 71.9, IQR 47.0–102.8) was associated with reduction in the risk of PE (OR 0.56, 95% CI 0.35–0.98, P = 0.04). The addition of PlGF:sEng to baseline characteristics non-significantly improved AUC from 0.78 to 0.82 ( P = 0.25) and improved reclassification of cases (NRI = 0.682, P = 0.002). Conclusions Screening tests incorporating first trimester sFlt-1 and second trimester PlGF:sEng have potential to aid PE prediction in high-risk pregnancies.

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Section: Discussioncontrasting

confidence: 54%

The role of biomarkers in predicting pre-eclampsia in high-risk women

et al. 2019

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“…For example, a sFlt‐1/PlGF ratio of 38 was found to effectively exclude preeclampsia with a negative predictive value (NPV) of 99.3% 7 ; however, a similar prospective study with Chinese pregnant women has yet to be published. Interestingly, a recent longitudinal study conducted in Singapore suggested significant differences in the PlGF and sFlt‐1 concentrations during pregnancy between different Asian ethnicities (Chinese, Malay, and Indian) 10 . In a retrospective study with 118 Chinese singleton pregnancies who had been diagnosed with preeclampsia, the sFlt‐1/PlGF ratio was shown to be an efficient marker in differentiating preeclampsia and predicting the timing of delivery for preeclampsia pregnancies 11 …”

Section: Introductionmentioning

confidence: 99%

Predictive values of various serum biomarkers in women with suspected preeclampsia: A prospective study

Wang

Hu²,

Liu

et al. 2021

Clinical Laboratory Analysis

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Background Preeclampsia (PE) prediction has been shown to improve the maternal and fetal outcomes in pregnancy. We aimed to evaluate the PE prediction values of a series of serum biomarkers. Methods The singleton pregnant women (20–36 gestational weeks) with PE‐related clinical and/or laboratory presentations were recruited and had the blood drawn at their first visits. The following markers were tested with the collected serum samples: soluble fms‐like tyrosine kinase 1 (sFlt‐1), placental growth factor (PlGF), thrombomodulin (TM), tissue plasminogen activator inhibitor complex (tPAI‐C), complement factors C1q, B, H, glycosylated fibronectin (GlyFn), pregnancy‐associated plasma protein‐A2 (PAPP‐A2), blood urea nitrogen (BUN), creatinine (Cre), uric acid (UA), and cystatin C (Cysc). Results Of the 196 recruited subjects, 25% (n = 49) developed preeclampsia before delivery, and 75% remained preeclampsia negative (n = 147). The serum levels of sFlt‐1, BUN, Cre, UA, Cysc, and PAPP‐A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia‐positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt‐1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP‐A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP‐A2). The positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%. Conclusions The serum markers investigated in current study showed better performance in ruling out than ruling in PE. Absence of pre‐defined latency period between blood draw and the onset of PE limits the clinical utility of these markers.

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“…12) The PPV was 30.3% (95% CI, 23.0-38.5) for ruling in PE within the next four weeks. 12) Since both sFlt-1 and PlGF concentrations, as well as the accuracy of the sFlt-1/PlGF ratio, could be influenced by ethnicity, 39,40) we conducted the current systematic review targeting only Japanese women.…”

Section: Discussionmentioning

confidence: 99%

Predictive Accuracy of Soluble FMS-Like Tyrosine Kinase-1/Placental Growth Factor Ratio for Preeclampsia in Japan: A Systematic Review

Yamazaki

Cerdeira

Agrawal

et al. 2021

Hypertens Res Pregnancy

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Preeclampsia is a major complication of pregnancy and is associated with significant fetal and maternal morbidity and mortality. Timely prediction of preeclampsia facilitates referral of potential patients to an adequate tertiary center, which helps reduce adverse outcomes associated with the disease. Moreover, by accurately ruling out preeclampsia, patients can be discharged safely and relieved of anxiety. Numerous candidate biomarkers have been proposed for the diagnosis and prediction of preeclampsia. Among these, maternal circulating factors such as soluble FMS-like tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor, and placental growth factor (PlGF), an angiogenic factor, are considered the most promising. Measuring these factors as a ratio allows assessment of the angiogenic imbalance that characterizes incipient or overt preeclampsia. The sFlt-1/PlGF ratio increases before the onset of preeclampsia and thus may help predict the disease. The test is used as a predictive tool in several countries but not yet routinely performed in Japanese hospitals.We performed a systematic review of studies that assessed the performance of the sFlt-1/PlGF ratio in predicting preeclampsia in Japanese patients. Three studies were included in the systematic review. All studies reported high negative predictive values of the sFlt-1/PlGF ratio (i.e., for ruling out PE), in agreement with the current evidence of the test performance worldwide. The sFlt-1/PlGF ratio could be of significant relevance in the Japanese population.

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Longitudinal circulating placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1) concentrations during pregnancy in Asian women: a prospective cohort study

Cited by 11 publications

References 20 publications

The role of biomarkers in predicting pre-eclampsia in high-risk women

The role of biomarkers in predicting pre-eclampsia in high-risk women

Predictive values of various serum biomarkers in women with suspected preeclampsia: A prospective study

Predictive Accuracy of Soluble FMS-Like Tyrosine Kinase-1/Placental Growth Factor Ratio for Preeclampsia in Japan: A Systematic Review

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