**3. Early diagnosis**

The aim for the early diagnosis is to start a preventive therapy by administration of 100mg acetylsalicylic acid (ASS, aspirin) before 16 weeks of pregnancy (reduction of risk for severe preeclampsia: RR 0.1; 95% KI 0.1–0.74) [26]. It is clear that a risk calculation in the first trimester would be the most effective method to prevent preeclampsia.

Since the data on the usefulness of early administration of aspirin is still emerging, the optimal dose, which is probably 70–160mg/d, is still under investigation. There is a known aspirin resistance in 33% of all women, which justifies the introduction of at least 100 instead of 80mg aspirin/d. The combination of aspirin and low-molecular-weight

#### *Prediction of Maternal and Fetal Syndrome of Preeclampsia*

heparin in secondary prevention seems to bring an additional benefit over aspirin alone [27], especially for an additional hereditary thrombophilia [28].

Early detection is based on three main points which are focused on and complement each other: a detailed medical history, the collection of biophysical parameters such as blood pressure, arterial stiffness, and Doppler examination of maternal blood vessels, and the determination of biochemical parameters, which can give clues to impaired placental function.

## **4. Maternal risk factors**

The risk factors that are involved in the development of preeclampsia are also the symptoms of the metabolic syndrome and glucose metabolism disorders such as diabetes mellitus as well as insulin resistance and assisted reproductive techniques, increased body mass index (>35kg/m2 ), and increased diastolic blood pressure > 80mmHg [29]. Further risk factors are positive preeclampsia of genetic background, multiple pregnancy, pregnancy above the age of 40, previous kidneyrelated problem, and coagulation problems [30, 31].

Specifically, prevalent coagulation problems connected with high risk of preeclampsia is factor V Leiden mutation, homozygous MTHFR mutation, hyperhomocysteinemia, existence of antiphospholipid antibodies, and the mixture of multiple thrombophilias [32].

Immune system cause-related problems can be ascribed to the high risk, for instance, in the first pregnancy. In contrast, multiparity with the same partner has lower risk [33].

As to record, 30% of women with preeclampsia are identified early with inaccurate positive rate of 5% [29]. As to the pregnancy-generated hypertension without preeclampsia, the motherly record is much more important than the maternal serum parameters and pulsatility indices of uterine arteries [34].

### **5. Parameters in biophysics**

Mean pressure of arterial blood in the first trimester can be implemented in pairs with risk factors of maternity as a predictor of preeclampsia in the first trimester that has a detection rate of 76% for early-onset preeclampsia. Systolic blood pressure is already substantially different in the first trimester regarding the early- and late-onset preeclampsia and pregnancy-generated hypertension [35].

The arterial supply to the uterus happens normally via uterine arteries, which change into circular running arteria arcuata. In this condition, the radial artery branches and spiral arteries move deeply into the myometrium and supply the decidua and fetus during pregnancy.

Anomalous placentation and incomplete cytotrophoblast invasion typified by inadequate formation and vasodilation of the spiral arteries have long been identified as one of the main risk factors for the growth of preeclampsia [36, 37].

These morphological changes indicate abnormal uteroplacental circulation typically characterized by a persistence of the postsystolic (Notch) and high resistance indices. A prediction of the severe form of pregnancy-induced hypertension and preeclampsia is possible by examining the uteroplacental vessels in the first and second trimesters. Various publications showed that in the first-trimester screening, Doppler examination of the uterine arteries identified a certain percentage of pregnant women that later develop preeclampsia with elevated uterine resistance indices and postsystolic incisions [38–40].

**25**

of pregnancy [52, 53].

*Risk Factor and Biomarker of Preeclampsia DOI: http://dx.doi.org/10.5772/intechopen.85173*

**6. Biochemical parameters**

the first trimester of pregnancy.

**6.1 PIGF (placental growth factor)**

genic factors such as PlGF [45].

41 and 59% and for late-onset preeclampsia 33% [51].

the first trimester [34].

About 40% of pregnant women can thus be detected at a false-positive rate of 5% [34, 41]. However, the sensitivity for the prediction of preeclampsia is significantly lower than that in the second-trimester ultrasound measurements. Higher rates of sensitivity regarding the discovery of a late-onset preeclampsia can be achieved in the second trimester of pregnancy. Several Doppler studies in the

The problem of the Doppler examination alone, however, lies in the low predictive value. Only in combination with biochemical markers, this evaluation is clinically relevant for a preventive therapy. In the second trimester, the combination of Doppler sonography and angiogenic factors such as PlGF/sEndoglin (sEng) and

In order to intervene preventively, high-risk population should be identified before the 16th week of pregnancy. The aim is, therefore, to predict preeclampsia at

PAPP-A was first identified as a predictive marker. PlGF is also in the first quarter of pregnancy decreased. Further promising targets for the first-trimester screening are PP-13, soluble endoglin, inhibin A, activin A, pentraxin 3, P-selectin, IGFBP-1 and IGFBP-3, adiponectin, resistin, l-arginine, asymmetric dimethylarginine (ADMA), and homoarginine. However, sFlt-1 is not suitable for screening in

PlGF belongs to the VEGF family, is secreted by trophoblast cells, and has proangiogenic function. Preeclampsia occurs due to an impaired placentation with subsequent ischemia triggers which raised secretion of antiangiogenic factors such as soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) in the circulation of maternity. This process creates a course of antagonizing the angio-

PIGF was in an early focus of the research groups in the search for a suitable prediction factor. It turned out that the concentration of PlGF in a preeclamptic pregnancy did not increase to the extent as would be expected in a normal pregnancy [46, 47]. Others could show that in the first trimester, there are already significant differences between PlGF concentrations in maternal blood of pregnant women with normal pregnancy and those that develop preeclampsia during pregnancy [34, 48–50]. Since 2011, the first conventional test of the company Alere allows the quantitative detection of PIGF in anticoagulated EDTA plasma in the first trimester with fluorescence immunoassay (sensitivity and specificity 95%). The detection rate of preeclampsia using PlGF alone for the early-onset preeclampsia is between

The latest studies show a strong connection between changed levels of PlGF and sVEGF R1 in preeclamptic pregnancy, as well as in those who will eventually develop the condition later in pregnancy. These reports are based on the findings that sVEGF R1 levels increase earlier and to a greater extent in women who eventually develop preeclampsia compared to women with normal pregnancies. In contrast, free PlGF levels in women who develop preeclampsia (compared to women with normal pregnancies) are meaningfully lower. Latest data indicate these markers to be convincing in the differential examinations of hypertensive diseases

second trimester yielded detection rates of 70–80% [42, 43].

sFlt-1 is a valid prediction of preeclampsia [44].

*Prediction of Maternal and Fetal Syndrome of Preeclampsia*

techniques, increased body mass index (>35kg/m2

related problem, and coagulation problems [30, 31].

clues to impaired placental function.

**4. Maternal risk factors**

multiple thrombophilias [32].

**5. Parameters in biophysics**

decidua and fetus during pregnancy.

indices and postsystolic incisions [38–40].

lower risk [33].

[27], especially for an additional hereditary thrombophilia [28].

heparin in secondary prevention seems to bring an additional benefit over aspirin alone

The risk factors that are involved in the development of preeclampsia are also the symptoms of the metabolic syndrome and glucose metabolism disorders such as diabetes mellitus as well as insulin resistance and assisted reproductive

pressure > 80mmHg [29]. Further risk factors are positive preeclampsia of genetic background, multiple pregnancy, pregnancy above the age of 40, previous kidney-

Specifically, prevalent coagulation problems connected with high risk of preeclampsia is factor V Leiden mutation, homozygous MTHFR mutation, hyperhomocysteinemia, existence of antiphospholipid antibodies, and the mixture of

Immune system cause-related problems can be ascribed to the high risk, for instance, in the first pregnancy. In contrast, multiparity with the same partner has

serum parameters and pulsatility indices of uterine arteries [34].

late-onset preeclampsia and pregnancy-generated hypertension [35].

As to record, 30% of women with preeclampsia are identified early with inaccurate positive rate of 5% [29]. As to the pregnancy-generated hypertension without preeclampsia, the motherly record is much more important than the maternal

Mean pressure of arterial blood in the first trimester can be implemented in pairs with risk factors of maternity as a predictor of preeclampsia in the first trimester that has a detection rate of 76% for early-onset preeclampsia. Systolic blood pressure is already substantially different in the first trimester regarding the early- and

The arterial supply to the uterus happens normally via uterine arteries, which change into circular running arteria arcuata. In this condition, the radial artery branches and spiral arteries move deeply into the myometrium and supply the

Anomalous placentation and incomplete cytotrophoblast invasion typified by inadequate formation and vasodilation of the spiral arteries have long been identi-

These morphological changes indicate abnormal uteroplacental circulation typically characterized by a persistence of the postsystolic (Notch) and high resistance indices. A prediction of the severe form of pregnancy-induced hypertension and preeclampsia is possible by examining the uteroplacental vessels in the first and second trimesters. Various publications showed that in the first-trimester screening, Doppler examination of the uterine arteries identified a certain percentage of pregnant women that later develop preeclampsia with elevated uterine resistance

fied as one of the main risk factors for the growth of preeclampsia [36, 37].

), and increased diastolic blood

Early detection is based on three main points which are focused on and complement each other: a detailed medical history, the collection of biophysical parameters such as blood pressure, arterial stiffness, and Doppler examination of maternal blood vessels, and the determination of biochemical parameters, which can give

**24**

About 40% of pregnant women can thus be detected at a false-positive rate of 5% [34, 41]. However, the sensitivity for the prediction of preeclampsia is significantly lower than that in the second-trimester ultrasound measurements. Higher rates of sensitivity regarding the discovery of a late-onset preeclampsia can be achieved in the second trimester of pregnancy. Several Doppler studies in the second trimester yielded detection rates of 70–80% [42, 43].
