Unit:
ΠΜΣ Έρευνα στη Γυναικεία ΑναπαραγωγήLibrary of the School of Health Sciences
Author:
Christofi Nikodimos
Supervisors info:
Ν. Σαλάκος, Αναπληρωτής Καθηγητής, Ιατρική,ΕΚΠΑ
Σ. Καλανταρίδου, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Γ. Μαστοράκος, Καθηγητής, Ιατρική, ΕΚΠΑ
Original Title:
Evaluation of serum pregnancy-associated plasma protein-A (PAPP-A) for first trimester prediction of preeclampsia: A systematic review
Translated title:
Evaluation of serum pregnancy-associated plasma protein-A (PAPP-A) for first trimester prediction of preeclampsia: A systematic review
Summary:
BACKGROUND: Preeclampsia is a pregnancy-related disease, characterized by de-novo development of hypertension and proteinuria after the 20th week of gestation; remains a leading cause of maternal mortality and morbidity. PE affects 2-8% of all pregnancies and 6% of all healthy nulliparous women with 93% of incidents developing at ≥34weeks. Despite the medical advances in perinatal care, there is still no reduction in the prevalence and the adverse outcomes of the disease due to the lack of understanding of the various pathophysiological mechanisms that can lead to its different subtypes. The early-onset (severe) PE is usually accompanied with FGR and placental lesions, revealing that placental impairment is the major contributor in the development of the disease. On the other hand, late-onset PE seems to be mainly related to maternal constitutional factors that affect the response to shallow placentation. PAPP-A is a syncytiotrophoblast-derived protease for an insulin-like growth factor binding protein, having key role in the IGF modulation.
PURPOSE: The identification of the performance characteristics of first trimester (11+0-13+6) serum PAPP-A MoMs for the prediction of preeclampsia that can justify or not its use as a screening tool in early antepartum monitoring. It is important to distinguish those high risk pregnancies at an early stage, so that with targeted interventions and close surveillance the incidence and complications of the disease can be reduced.
METHODOLOGY: A systematic review based on literature search of electronic databases in order to identify published studies relevant to the subject.
RESULTS: The systematic review yielded 539 citations and after screening the title and abstract and removing duplicate citations, 72 were assessed on full text. Further exclusion of 59 studies due to various issues; leave 13 to be included in this review. The mean sensitivity of PAPP-A MoM in the prediction of preeclampsia is low (14.1% and 22.5% at fixed specificity of 95% and 90% respectively) which is consistent with previous published results. For the prediction of EOPE the respective mean sensitivities were slightly higher (19.3% and 24.1%). When PAPP-A MoMs were combined with maternal risk factors the mean sensitivities were found to be more than double at the same specificity rates. Moreover, published predictive models combining maternal factors, PAPP-A MoMs with other biomarkers (PP13, PlGF, inhibin-A, etc.) and biophysical markers (MAP, UtA-PI) yielded sensitivity rates of almost 85%. Regression analyses revealed same findings using the AUC values. The results regarding the association of low serum PAPP-A MoM levels with the prediction of LOPE are inconsistent; maternal characteristics alone are found to be the major contributor for the prediction of LOPE and no improvement in the overall prediction was observed by the addition of any first trimester markers.
CONCLUSIONS: The predictive performance of first trimester maternal serum PAPP-A MoMs when used as a single marker is poor; even though there is a significant association of its low levels with adverse outcomes regarding inadequate placental invasion (PE, EOPE, FGR). The predictive performance is improved when PAPP-A MoMs are combined with maternal risk factors, MAP, UtA-PI and other biochemical markers such as PlGF and inhibin-A. None of the first trimester biomarkers studied so far can be validated as a single predictor of preeclampsia. The smaller prediction found for LOPE and GH indicates the different etiology of these outcomes. Overall, further investigation should take place in order to detect novel biochemical markers with better predictive characteristics that could be translated into clinical practice.
Main subject category:
Health Sciences
Keywords:
Preeclampsia, PAPP-A, Hypertension disorders of pregnancy
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