Taiwanese new direction in prediction of early pregnancy preeclampsia: a prospective and non-interventional study

Abstract Background First trimester screening is essential to preeclampsia (PE) prevention. Fetal Medicine Foundation (FMF) model combined maternal characteristics with mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI) and placental growth factor (PlGF) to estimate risk. High detection rate (DR) was observed in Asia. The study aims to evaluate performance of screening in Taiwan.Methods This was a prospective and non-interventional study between January, 2017 and June, 2018. Data was collected from 700 pregnant women at 11+ 0-13+ 6 gestational week. Maternal characteristics were recorded. MAP, UtAPI and PlGF were measured and converted into Multiple of the Median (MoM). Patient-specific risks were calculated with FMF model. Performance of screening was examined by ROC curve and DR.Results 25 women (3.57%) contracted PE, including 8 with preterm PE (1.14%). In preterm PE, mean MoM of MAP and UtAPI were higher (1.096 vs 1.000; 1.084 vs 1.035). Mean MoM of PlGF was lower (0.927 vs 1.031). DR in preterm PE achieved 12.5%, 50.0%, 50.0% and 62.5% at false-positive rate (FPR) of 5%, 10%, 15% and 20%.Conclusion FMF model showed high DR for PE in Taiwan. Integration of PE and Down screening could set up a one-step workflow.

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First trimester Down's syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free β human chorionic gonadotophin, pregnancy-associated plasma protein-A and nuchal translucency

Journal of Medical Screening ◽

10.1258/jms.2008.008049 ◽

2008 ◽

Vol 15 (4) ◽

pp. 204-206 ◽

Cited By ~ 16

Author(s):

Jonathan P Bestwick ◽

Wayne J Huttly ◽

Nicholas J Wald

Keyword(s):

Meta Analysis ◽

False Positive Rate ◽

Protein A ◽

First Trimester ◽

Nuchal Translucency ◽

Screening Performance ◽

Combined Test ◽

Positive Rate ◽

Trimester Screening ◽

Β Hcg

Objectives To examine the effect of smoking on three first trimester screening markers for Down's syndrome that constitute the Combined test, namely nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free β human chorionic gonadotophin (free β-hCG) and to use the results to determine which of these markers need to be adjusted for smoking and by how much. Methods The difference in the median multiple of the median (MoM) values in smokers compared to non-smokers was determined for NT, PAPP-A and free β-hCG in 12,517 unaffected pregnancies that had routine first trimester Combined test screening. These results were then included in a meta-analysis of published studies and the effect of adjusting for smoking on screening performance of the Combined test was estimated. Results The results using the routine screening data were similar to the summary estimates from the meta-analysis of all studies. The results from the meta-analysis were; median MoM in smokers compared to non-smokers: 1.06 NT (95% confidence interval 1.03 to 1.10), 0.81 PAPP-A (0.80 to 0.83) and 0.94 free β-hCG (0.89 to 0.99). The effect of adjusting for smoking on the Combined test is small, with an estimated less than half percentage point increase in the detection rate (the proportion of affected pregnancies with a positive result) for a 3% false-positive rate (the proportion of unaffected pregnancies with a positive result) and less than 0.2 percentage point decrease in the false-positive rate for an 85% detection rate. Conclusion Adjusting first trimester screening markers for smoking has a minimal favourable effect on screening performance, but it is simple to implement and this paper provides the adjustment factors needed if a decision is made to make such an adjustment.

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New screen on the block: non-invasive prenatal testing for fetal chromosomal abnormalities

Journal of Primary Health Care ◽

10.1071/hc16055 ◽

2017 ◽

Vol 9 (4) ◽

pp. 248 ◽

Cited By ~ 1

Author(s):

Sara Filoche ◽

Beverley Lawton ◽

Angela Beard ◽

Anthony Dowell ◽

Peter Stone

Keyword(s):

False Positive ◽

Chromosomal Abnormalities ◽

False Positive Rate ◽

Prenatal Testing ◽

Diagnostic Procedures ◽

First Trimester ◽

Maternal Blood ◽

Non Invasive ◽

Positive Rate ◽

Trimester Screening

ABSTRACT Non-invasive prenatal testing (NIPT) is a new screen for fetal chromosomal abnormalities. It is a screening test based on technology that involves the analysis of feto-placental DNA that is present in maternal blood. This DNA is then analysed for abnormalities of specific chromosomes (eg 13, 18, 21, X, Y). NIPT has a much higher screening capability for chromosomal abnormalities than current combined first trimester screening, with ~99% sensitivity for trisomy 21 (Down syndrome) and at least a 10-fold higher positive predictive value. The low false-positive rate (1–3%) is one of the most advertised advantages of NIPT. In practice, this could lead to a significant reduction in the number of false-positive tests and the need for invasive diagnostic procedures. NIPT is now suitable for singleton and twin pregnancies and can be performed from ~10 weeks in a pregnancy. NIPT is not currently publicly funded in most countries. However, the increasing availability of NIPT commercially will likely lead to an increase in demand for this as a screening option. Given the high numbers of women who visit a general practitioner (GP) in their first trimester, GPs are well-placed to also offer NIPT as a screening option. A GP’s role in facilitating access to this service will likely be crucial in ensuring equity in access to this technology, and it is important to ensure that they are well supported to do so.

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First trimester screening for pre-eclampsia

Obstetric Medicine ◽

10.1177/1753495x16649074 ◽

2016 ◽

Vol 9 (3) ◽

pp. 106-112 ◽

Cited By ~ 5

Author(s):

Stefan C Kane

Keyword(s):

Clinical Utility ◽

Disease Burden ◽

False Positive Rate ◽

First Trimester ◽

Detection Rates ◽

Positive Rate ◽

Trimester Screening ◽

First Trimester Of Pregnancy ◽

Different Populations ◽

Further Development

The commercial availability of tests in the first trimester of pregnancy that predict the later development of pre-eclampsia has prompted considerable debate regarding their clinical utility and the degree to which they fulfil the longstanding principles of screening. Such tests have been shown to achieve detection rates for early pre-eclampsia (requiring delivery prior to 34 weeks) of over 90%, for a false positive rate of 10%. However, their capacity to predict later onset pre-eclampsia, which accounts for the bulk of the disease burden, is much more limited. The relatively few studies validating the performance of these tests in different populations have demonstrated significant variations in performance. Moreover, prospective research confirming that the administration of aspirin to those screened to be high risk reduces the incidence of pre-eclampsia is yet to be completed, and there may be harms in restricting aspirin therapy to this group, given its broader beneficial effect. In light of these limitations, further development of these tests is recommended prior to their introduction to clinical practice.

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Ductus Venosus: A Love Story of 14 Years

Donald School Journal of Ultrasound in Obstetrics & Gynecology ◽

10.5005/jp-journals-10009-1190 ◽

2011 ◽

Vol 5 (2) ◽

pp. 141-149 ◽

Cited By ~ 1

Author(s):

Nuno Montenegro ◽

Alexandra Matias

Keyword(s):

Blood Flow ◽

Chromosomal Abnormalities ◽

False Positive Rate ◽

First Trimester ◽

Nuchal Translucency ◽

Ductus Venosus ◽

Love Story ◽

Positive Rate ◽

Trimester Screening ◽

Twin Pregnancies

ABSTRACT Ductus venosus is a tiny vessel with a central role in fetal circulation. Combining B-mode with color and pulsed Doppler is feasible to identify this vessel and evaluate the blood flow waveform at 11 to 13 weeks. The higher prevalence of abnormal A-wave in fetuses with abnormal karyotype and/or cardiac defects turned DV evaluation into a useful marker for chromosomal abnormalities and cardiopathies. Even when combined with nuchal translucency (NT) or biochemical markers, DV blood flow evaluation contributes to an increase in sensitivity and reduces false-positive rate. Abnormal ductal flow is also related to a worse fetal and perinatal outcome. In monochorionic twin pregnancies, in addition to NT measurement at 11 to 14 weeks, the Doppler assessment of DV blood flow increases relevantly the performance of screening for those at higher risk of developing twin-to-twin transfusion syndrome. This story of 14 years surely contributed to change the way first trimester screening is being implemented.

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Combined First-Trimester Screening in Northern Finland: Experiences of the First Ten Years

Clinical Medicine Insights Reproductive Health ◽

10.4137/cmrh.s14958 ◽

2014 ◽

Vol 8 ◽

pp. CMRH.S14958

Author(s):

Merilainen Anna ◽

Peuhkurinen Sini ◽

Honkasalo Timppa ◽

Laitinen Paivi ◽

Kokkonen Hannaleena ◽

...

Keyword(s):

Detection Rate ◽

False Positive Rate ◽

Down's Syndrome ◽

Down’S Syndrome ◽

First Trimester ◽

First Trimester Screening ◽

Invasive Procedures ◽

Screening Performance ◽

Positive Rate ◽

Trimester Screening

Objective To evaluate the efficacy of first trimester combined screening for Down's syndrome in Northern Finland during the first 10 years of practice. Methods During 1 January 2002 to 31 December 2011, 47,896 women participated voluntarily in combined screening during first trimester. The risk cutoff was 1:250. The study period was divided into two time periods; 2002-2006 and 2007-2011. Results During the first half of the study period, the detection rate (DR) was 77.3% with a 4.9% false-positive rate (FPR). During the latter half, the DR was 77.1% with a 2.8% FPR. Conclusions An important issue is the number of invasive procedures needed to detect one case of Down's syndrome. The screening performance improved markedly in the latter five years period since the FPR lowered from 4.9% to 2.8% and the number of invasive procedures needed to detect one case of Down's syndrome lowered from 15 to 11.

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First-Trimester Uterine Artery Doppler for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndrome Study

American Journal of Perinatology ◽

10.1055/s-0038-1675209 ◽

2018 ◽

Vol 36 (09) ◽

pp. 930-935

Author(s):

Suzanne Demers ◽

Amélie Boutin ◽

Cédric Gasse ◽

Olivier Drouin ◽

Mario Girard ◽

...

Keyword(s):

Gestational Age ◽

Uterine Artery ◽

Prediction Models ◽

False Positive Rate ◽

First Trimester ◽

Maternal Characteristics ◽

Receiver Operating Characteristic Curves ◽

Nulliparous Women ◽

Positive Rate

Objective This study aimed to estimate the performance of first-trimester uterine artery (UtA) pulsatility index (PI) for the prediction of preeclampsia (PE). Study Design We conducted a prospective cohort study of nulliparous women with singleton gestation at 11 to 13 6/7 weeks. UtA-Doppler's was performed on both UtAs and the mean UtA-PI was reported in multiple of median (MoM) adjusted for gestational age. Using receiver operating characteristic curves and their area under the curves (AUC); we calculated the performance of UtA-PI for the prediction of PE. Proportional hazard models were used to develop prediction models combining UtA-PI and maternal characteristics. Results Out of 4,676 participants with completed follow-up, 232 (4.9%) developed PE, including 202 (4.3%) term and 30 (0.6%) preterm PE. Mean UtA-PI decreased with gestational age between 11 and 13 6/7 weeks (p < 0.001). First-trimester UtA-PI was associated with preterm (AUC: 0.69; 95% CI [confidence interval]: 0.57–0.80) but not with term (AUC: 0.52; 95% CI: 0.48–0.56) PE. UtA-PI combined with maternal characteristics could predict 45% of preterm PE at a false positive rate of 10%. Conclusion First-trimester UtA-PI decreases with gestational age between 11 and 13 6/7 weeks and is associated with the risk of preterm but not term PE.

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Combined screening test for trisomy 21 – is it as efficient as we believe?

Journal of Perinatal Medicine ◽

10.1515/jpm-2016-0031 ◽

2017 ◽

Vol 45 (2) ◽

Cited By ~ 3

Author(s):

Marcin Wiechec ◽

Agnieszka Nocun ◽

Anna Knafel ◽

Ewa Wiercinska ◽

Jiri Sonek ◽

...

Keyword(s):

Trisomy 21 ◽

Absolute Risk ◽

False Positive Rate ◽

First Trimester ◽

First Trimester Screening ◽

Screening Performance ◽

The Us ◽

Positive Rate ◽

Trimester Screening ◽

The One

AbstractObjectives:To compare two first-trimester screening strategies: traditional combined screening and the one based on ultrasound markers only. We investigated the effect of maternal age (MA) on the screening performance of both of these strategies.Methods:This was a prospective observational study based on a non-selected mixed-risk population of 11,653 women referred for first-trimester screening. The study population was divided in two groups: combined screening (CS) and ultrasound-based screening (US). Absolute risk was calculated to determine the influence of MA on screening performance.Results:The CS arm comprised 5145 subjects including 51 cases of trisomy 21 (T21), and the US arm comprised 5733 subjects including 87 subjects with T21. Seven hundred and seventy-five subjects were excluded from the study. For a false positive rate (FPR) of 3%, the detection rate (DR) of T21 in CS arm was 78% vs. 90% in US arm. For 5% FPR, DR was 84% and 94% in CS and US arm, respectively. MA had an influence on DR positive rates in CS: both DR and FPR for T21 increased with advance in MA.Conclusions:The US protocol showed higher DR of T21 compared to the CS one. It may be considered as a viable alternative to CS for T21 where access to biochemical testing is limited.

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Cell-free DNA Testing: Where are We now?

Donald School Journal of Ultrasound in Obstetrics & Gynecology ◽

10.5005/jp-journals-10009-1463 ◽

2016 ◽

Vol 10 (2) ◽

pp. 172-177

Author(s):

Gokhan Goynumer ◽

Cihat Sen ◽

Olus Api ◽

Murat Yayla

Keyword(s):

Maternal Age ◽

Detection Rate ◽

False Positive Rate ◽

First Trimester ◽

First Trimester Screening ◽

Dna Testing ◽

Clinical Implementation ◽

Free Dna ◽

Positive Rate ◽

Trimester Screening

ABSTRACT Prenatal screening for fetal aneuploidies has been focused on mainly Down syndrome in the last 40 years. The method of screening has changed from maternal age in the 1970s, with a detection rate of 30 and 5% false positive rate (FPR), to a combination of maternal age and second-trimester serum biochemical markers (triple test and quadruple test) in the 1980s and 1990s, with 60 to 75% detection rate and 5% false positive rate (FPR). Following this, the era of first trimester screening for Down syndrome has started with the clinical implementation of fetal nuchal translucency screening. The combination of maternal age, NT thickness and serum free beta-human chorionic gonadotropin (â-hCG) and pregnancy-associated plasma protein A (PAPP-A) in the first trimester has yielded a 90% detection rate with a 5% FPR. Starting from the year 2008, studies have shown that the performance of screening may be improved by analysis of cell-free deoxyribonucleic acid (DNA) (cfDNA) in maternal blood. Several studies in the last few years have reported the clinical validation of cell free fetal DNA test in the maternal serum in screening for trisomies 21, 18, and 13 and sex chromosome aneuploidies. Its widespread use is limited by the relatively high cost of the test and the lack of consensus about the optimal way for its clinical implementation. Until the optimal way of incorporating cfDNA into the clinical practice gets identified, it would be wise not to substitute cfDNA testing in place of first-trimester screening for fetal defects and other major complications of pregnancy. Furthermore, it would be preferable for clinicians managing individual patients not to counsel them for their result as positive or negative, rather the clinicians should use the risk estimate from the first-line method of screening as the prior risk and modify this by the appropriate positive or negative likelihood ratio from the cfDNA test. How to cite this article Sen C, Api O, Yayla M, Goynumer G. Cell-free DNA Testing: Where are We now? Donald School J Ultrasound Obstet Gynecol 2016;10(2):172-177.

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Simple approach based on maternal characteristics and mean arterial pressure for the prediction of preeclampsia in the first trimester of pregnancy

Journal of Perinatal Medicine ◽

10.1515/jpm-2016-0418 ◽

2017 ◽

Vol 45 (7) ◽

Cited By ~ 7

Author(s):

Rebeca Silveira Rocha ◽

Júlio Augusto Gurgel Alves ◽

Sammya Bezerra Maia e Holanda Moura ◽

Edward Araujo Júnior ◽

Alberto Borges Peixoto ◽

...

Keyword(s):

Predictive Value ◽

Skin Color ◽

Characteristic Curve ◽

False Positive Rate ◽

First Trimester ◽

Maternal Characteristics ◽

Arterial Blood ◽

Positive Rate ◽

History Of ◽

First Trimester Of Pregnancy

AbstractAim:To propose a simple model for predicting preeclampsia (PE) in the 1Methods:A prospective cohort was performed to predict PE between 11 and 13+6 weeks of gestation. The MC evaluated were maternal age, skin color, parity, previous PE, smoking, family history of PE, hypertension, diabetes mellitus and body mass index (BMI). Mean arterial blood pressure (MAP) was measured at the time of the 1Results:We analyzed 733 pregnant women; 55 developed PE, 21 of those developed preterm PE and 34 term PE. For total PE, the best model was MC+MAP, which had an area under the receiver operating characteristic curve (AUC ROC) of 0.79 [95% confidence interval (CI)=0.76–0.82]. For preterm PE, the best model was MC+MAP, with an AUC ROC of 0.84 (95% CI=0.81–0.87). For term PE, the best model was MC, with an AUC ROC of 0.75 (0.72–0.79). The MC+MAP model demonstrated a detection rate of 67% cases of preterm PE, with a false-positive rate of 10%, positive predictive value of 17% and negative predictive value of 99%.Conclusion:The MC+MAP model showed good accuracy in predicting preterm PE in the 1

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