A novel approach to first-trimester screening for early pre-eclampsia combining serum PP13 and Doppler ultrasound

Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
Ultrasound in Obstetrics and Gynecology (Impact Factor: 3.85). 12/2005; 27(1):13-17. DOI: 10.1002/uog.2686
Source: PubMed


To investigate the value of maternal serum placental protein 13 (PP-13) measurement and uterine artery Doppler during first-trimester screening in the prediction of early pre-eclampsia.
This was a nested case-control prospective study of pregnancies at 11 + 0 to 13 + 6 weeks of gestation. The pulsatility index (PI) of blood flow in the uterine arteries and the maternal serum concentration of PP-13 were measured in 10 women who went on to develop pre-eclampsia that necessitated delivery before 34 weeks, and in 423 unaffected women. Results were expressed as multiples of the gestation-specific median in controls (MoM). A logistic regression model was used to predict detection and false-positive rates.
In the cases that developed pre-eclampsia requiring delivery before 34 weeks, compared with the unaffected pregnancies, the median uterine artery PI was higher (1.43 MoM) and the median serum PP-13 level was lower (0.07 MoM; P < 0.001, Wilcoxon rank sum test for both). Modeling predicted that for a 90% detection rate of pre-eclampsia requiring delivery before 34 weeks, the false-positive rate of screening by PP-13 was 12%, by uterine artery PI was 31% and by a combination of the two methods was 9%. A policy of contingency screening, whereby all women are screened by maternal serum PP-13 and only the 14% at highest risk are then screened by Doppler, achieved a detection rate of 90% with an overall false-positive rate of 6%.
Effective screening for pre-eclampsia requiring delivery before 34 weeks can potentially be provided by assessment of a combination of maternal serum PP-13 and uterine artery Doppler in the first trimester of pregnancy.

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    • "PP13, which is exclusively produced by placental tissue, possesses a conserved carbohydrate binding domain, to which two proteins Annexin-II and Actin-beta bind. These proteins are considered to play a key role in placentation and maternal artery remodelling respectively19. "
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    ABSTRACT: Pre-eclampsia (PE) is a pregnancy related disorder characterized by hypertension and proteinuria noticeable after 20 wk of gestation. It is a leading cause of maternal and foetal mortality and morbidity worldwide. The aetiology of the disease is unknown, but recent studies have revealed that this disorder appears to originate in placenta and is characterized by widespread maternal endothelial dysfunction. Till date, delivery of placenta is the only cure for the disease. So, there is a need for the identification of highly specific and sensitive biochemical markers that would allow early identification of patients at risk and thus help in providing proper prenatal care. Several promising biomarkers have been proposed, alone or in combination, that may help in predicting women who are likely to develop PE. Maternal serum concentrations of these biomarkers either increase or decrease in PE during gestation. This review focuses on the various biomarkers available and their utility in predicting pre-eclampsia.
    The Indian Journal of Medical Research 07/2013; 138(1):60-7. · 1.40 Impact Factor
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    • "In the study of Nicloides et al. in patients with pregnancy termination due to severe preeclampsia before week 34, the PP13 serum levels were lower than the normotensive individuals [5]. A retrospective study showed that PP13 levels in weeks 5 and 6 of pregnancy are associated with incidence of preeclampsia [6]. "
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    ABSTRACT: Background. Preeclampsia affects 5-6% of all pregnancies. Predictive factors of preeclampsia can be helpful in early diagnosis of this disease. In this study the predictive values of biochemical markers placenta protein 13 (PP13) and pregnancy-associated plasma protein A (PAPP-A) have been assessed in early diagnosis of preeclampsia. Methods. This case-control study was conducted on 1500 women who presented to a healthcare center of Sari, Iran, between 2010 and 2011. Blood samples were drawn in weeks 11–13 and 24–28 of pregnancy. Of them who developed preeclampsia were considered as case group. A control group consisted of similar women regarding mean age, body mass index (BMI), and pregnancy age. PAPP-A and PP13 serum levels were measured. Data were analyzed using proper statistical tests. Results. PAPP-A and PP13 serum levels were significantly lower in both the first and second trimesters in women who developed preeclampsia (P < 0.001). The cumulative value of all four variables with cut-off point of 238.5 has sensitivity, specificity of 91.0%, and undercurve surface of 0.968 which is the most diagnostic value for preeclampsia. Conclusion. It is possible to advantage measuring of PAPP-A and PP13 in the first and second trimesters especially their cumulative values in both trimesters for prediction of the incidence of preeclampsia.
    ISRN obstetrics and gynecology 06/2012; 2012:263871. DOI:10.5402/2012/263871
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    • "At a false positive rate of 10%, PP13 showed a prediction rate of 80% as a single biochemical marker. In combination with Doppler ultrasound PI, the prediction rate increased to 90% [41]. PP13 has also been used in combination with PAPP-A. "
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    ABSTRACT: Worldwide the prevalence of preeclampsia (PE) ranges from 3 to 8% of pregnancies. 8.5 million cases are reported yearly, but this is probably an underestimate due to the lack of proper diagnosis. PE is the most common cause of fetal and maternal death and yet no specific treatment is available. Reliable biochemical markers for prediction and diagnosis of PE would have a great impact on maternal health and several have been suggested. This review describes PE biochemical markers in general and first trimester PE biochemical markers specifically. The main categories described are angiogenic/anti-angiogenic factors, placental proteins, free fetal hemoglobin (HbF), kidney markers, ultrasound and maternal risk factors. The specific biochemical markers discussed are: PAPP-A, s-Flt-1/PlGF, s-Endoglin, PP13, cystatin-C, HbF, and α₁-microglobulin (A1M). PAPP-A and HbF both show potential as predictive biochemical markers in the first trimester with 70% sensitivity at 95% specificity. However, PAPP-A is not PE-specific and needs to be combined with Doppler ultrasound to obtain the same sensitivity as HbF/A1M. Soluble Flt -1 and PlGF are promising biochemical markers that together show high sensitivity from the mid-second trimester. PlGF is somewhat useful from the end of the first trimester. Screening pregnant women with biochemical markers for PE can reduce unnecessary suffering and health care costs by early detection of mothers at increased risk for PE, thus avoiding unnecessary hospitalization of pregnant women with suspect or mild PE and enabling monitoring of the progression of the disease thereby optimizing time for delivery and hopefully reducing the number of premature births.
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