**4. Symptoms**

Preeclampsia sometimes develops without any symptoms. High blood pressure may develop slowly, or it may have a sudden onset. Monitoring of blood pressure is an important part of prenatal care because the first sign of preeclampsia is commonly a rise in blood pressure. Blood pressure that exceeds 140/90 mmHg documented on two occasions, at least 4 h apart—is considered abnormal.

Other signs and symptoms of preeclampsia may include:


Many of these symptoms also occur in normal pregnancies, so they are not considered reliable signs of preeclampsia though they will alert the obstetrician.

The International Society of Study of Hypertension in Pregnancy (ISSHP) recently suggested that a clinical diagnosis is made even in the absence of proteinuria if organ-specific signs or symptoms are present with new onset of hypertension [12].

Hemolysis, abnormal elevation of liver enzymes levels, and low platelet count occur together as the HELLP syndrome [13]. HELLP syndrome is a severe variant of preeclampsia that occurs in 5% of cases and can progress rapidly to a lifethreatening condition [14]. The presence of seizures in preeclampsia is eclampsia and is another complication during pregnancy and at delivery. In **Table 1**, diagnostic criteria are summarized.

**63**

can control.

*Clinical, Biochemical, and Biophysical Markers of Angiogenesis in Preeclampsia*

• Greater than or equal to 140 mm Hg systolic or greater than or equal to 90 mm Hg diastolic on two occasions at least 4 h apart after 20 weeks of gestation in a woman with a previously normal blood pressure • Greater than or equal to 160 mm Hg systolic or greater than or equal to 110 mm Hg diastolic; hypertension

can be confirmed within a short interval (minutes) to facilitate timely antihypertensive therapy

• Greater than or equal to 300 mg per 24 h urine collection (or this amount extrapolated from a timed

Or in the absence of proteinuria, new-onset hypertension with the new onset of any of the following:

• Serum creatinine concentrations greater than 1.1 mg/dL or a doubling of the serum creatinine concentration

*DOI: http://dx.doi.org/10.5772/intechopen.85732*

• Protein/creatinine ratio greater than or equal to 0.3\*

• Dipstick reading of 1+ (used only if other quantitative methods not available)

(normal levels in pregnancy are 0.8 mg/dL) in the absence of other renal disease

• Elevated blood concentrations of liver transaminases to twice normal concentration

**Blood pressure**

and

or

**Proteinuria**

collection)

**Thrombocytopenia**

**Renal insufficiency**

**Impaired liver function**

Cerebral or visual symptoms

**Pulmonary edema**

*Each measured as mg/dL.*

*\**

**Table 1.**

• Platelet count less than 100,000/μl

**5. Risk factors of preeclampsia**

*Diagnostic criteria for preeclampsia by ACOG.*

eclampsia can be prevented.

increase the risk for high blood pressure.

**Risk factors High risk factors**

Age > 40 years Chronic kidney disease BMI > 30 kg/m2 Diabetes mellitus Family history of PE Chronic hypertension History of previous pregnancy with PE Autoimmune disease

Risk factors include health conditions, lifestyle, and family history that can

Some medical conditions can raise the risk for high blood pressure. If one of these risks is present, the pregnant women can take steps to control it and lower the risk. However preeclampsia cannot be prevented, but the complications of pre-

**ACOG recommendation, any risk factor [1] NICE guidelines, one high risk or two moderate risk factors [15]**

Nulliparity Hypertensive disease in previous pregnancy

Some of the risk factors for high blood pressure cannot be controlled, such as age or family history. But we can take steps to lower our risk by changing the factors we


#### **Table 1.**

*Prediction of Maternal and Fetal Syndrome of Preeclampsia*

**4. Symptoms**

reversible encephalopathy syndrome (PRES), refractory neurological disorders, or even eclampsia. In kidney, the depletion of vascular endothelial growth factor (VEGF) in the podocytes leads to endotheliosis, and these block the slit diaphragms in the basement membrane, exacerbating the already decreased glomerular filtration and causing proteinuria. Finally, endothelial dysfunction promotes microangiopathic hemolytic anemia, and vascular hyperpermeability associated with low serum albumin causes edema, particularly in the lower limbs or lungs. The crucial issue to understand is that

Preeclampsia sometimes develops without any symptoms. High blood pressure may develop slowly, or it may have a sudden onset. Monitoring of blood pressure is an important part of prenatal care because the first sign of preeclampsia is commonly a rise in blood pressure. Blood pressure that exceeds 140/90 mmHg documented on two occasions, at least 4 h apart—is considered abnormal.

the prime mover of preeclampsia is abnormal placentation [11] [**Figure 2**].

Other signs and symptoms of preeclampsia may include:

• Upper abdominal pain, usually under ribs on the right side

• Decreased levels of platelets in the blood (thrombocytopenia)

Many of these symptoms also occur in normal pregnancies, so they are not considered reliable signs of preeclampsia though they will alert the obstetrician. The International Society of Study of Hypertension in Pregnancy (ISSHP)

Hemolysis, abnormal elevation of liver enzymes levels, and low platelet count occur together as the HELLP syndrome [13]. HELLP syndrome is a severe variant of preeclampsia that occurs in 5% of cases and can progress rapidly to a lifethreatening condition [14]. The presence of seizures in preeclampsia is eclampsia and is another complication during pregnancy and at delivery. In **Table 1**, diagnos-

recently suggested that a clinical diagnosis is made even in the absence of proteinuria if organ-specific signs or symptoms are present with new onset of

• Vision changes include sensations of flashing lights, light sensitivity,

• Excess protein in urine (proteinuria)

• Severe headaches

blurry vision, or spots

• Nausea or vomiting

• Decreased urine output

• Impaired liver function

• Sudden weight gain

• Swelling (edema)

hypertension [12].

tic criteria are summarized.

• Shortness of breath and anxiety

**62**

*Diagnostic criteria for preeclampsia by ACOG.*

### **5. Risk factors of preeclampsia**

Risk factors include health conditions, lifestyle, and family history that can increase the risk for high blood pressure.

Some of the risk factors for high blood pressure cannot be controlled, such as age or family history. But we can take steps to lower our risk by changing the factors we can control.

Some medical conditions can raise the risk for high blood pressure. If one of these risks is present, the pregnant women can take steps to control it and lower the risk. However preeclampsia cannot be prevented, but the complications of preeclampsia can be prevented.



*ACOG, American College of Obstetricians and Gynecologists; NICE, National Institute of Clinical Excellence; PE, preeclampsia*

#### **Table 2.**

*Risk factors for preeclampsia by ACOG and NICE recommendations.*

Preeclampsia develops only as a complication of pregnancy. Risk factors are presented in **Table 2** together with data of increased risk for some items [15].

The National Institute for Health and Care Excellence (NICE) recommends that women with high and more than one of the moderate risk factors for preeclampsia should be advised to take aspirin from 12 weeks gestation [16].

### **6. Biochemical markers**

The role of biomarkers in preeclampsia diagnosis is becoming increasingly important. A literature review gives us a range of biomarkers that have proved to be sufficiently specific and sensitive to be classified as potential biomarkers (**Figure 3**). The most researched with data on specificity and sensitivity are given in **Table 3**. A good biomarker would be one, which may have the potential of identifying women earlier in their disease course. There have been also many studies investigating multiple-marker algorithms for predicting preeclampsia.

#### **Figure 3.**

*Biochemical markers in preeclampsia. sFlt-1, soluble fms-like tyrosine kinase 1; PlGF, placental growth factor; sEng, soluble endoglin; PP13, placental protein 13; PAPP-A, pregnancy-associated plasma protein A.*

**65**

**Figure 4.**

*endothelial dysfunction.*

*Clinical, Biochemical, and Biophysical Markers of Angiogenesis in Preeclampsia*

**Biomarker Sensitivity Specificity** sFlt-1 26–73.1% 88.5–100% PlGF 64.1% 89.5% sFlt-1/ PlGF 78% 84% sEng 18–85% 69–84.6% PP13 79–100% 80–90% PAPP-A 1st trimester 49.7–69.7% 68.6–85.7% NGAL 97.89% 93.55% Insulin resistance 73% 85% SHBG 85% 37.7% Inhibin A and activin A 87% 80% Copeptin 1st trimester 88% 81%

*DOI: http://dx.doi.org/10.5772/intechopen.85732*

**6.1 Soluble fms-like tyrosine kinase 1 (sFlt-1)**

*Biomarker test characteristics for prediction.*

**6.2 Placental growth factor**

**Table 3.**

Soluble Flt-1 is an anti-angiogenic form of VEGF receptor 1. sFlt-1 acts as a potent scavenger of VEGF and PlGF (**Figure 4**), thus preventing their interaction with endothelial receptors on the cell surface, and subsequently induces endothelial dysfunction. Elevated concentration of sFlt-1 has been as early as 5 weeks before the diagnosis of preeclampsia and correlates with severity of disease [17, 18]. Some other studies also support this sFlt-1 role in the pathogenesis of preeclampsia [19–21].

Podocytes 38–100% 70–100% *sFlT-1, soluble fms-like tyrosine kinase 1; NGAL, neutrophil gelatinase-associated lipocalin; PAPP, pregnancyassociated plasma protein; PP, placental protein; sEng, soluble endoglin; SHBG, sex hormone-binding globulin*

Uterine artery Doppler Positive likelihood ratio 9:1

Placental growth factor (PlGF) is a prominent angiogenic factor in the development of the placental vascular system [22, 23]. During normal pregnancy, PlGF can

*Circulating sFlt-1 in the maternal blood leads to a net decrease in PlGF and VEGF in the vasculature, which are necessary for normal placental angiogenesis. In PE angiogenic balance is disturbed and may result in* 


*Clinical, Biochemical, and Biophysical Markers of Angiogenesis in Preeclampsia DOI: http://dx.doi.org/10.5772/intechopen.85732*

*sFlT-1, soluble fms-like tyrosine kinase 1; NGAL, neutrophil gelatinase-associated lipocalin; PAPP, pregnancyassociated plasma protein; PP, placental protein; sEng, soluble endoglin; SHBG, sex hormone-binding globulin*

#### **Table 3.**

*Prediction of Maternal and Fetal Syndrome of Preeclampsia*

Chronic hypertension **Moderate risk factors**

Systemic lupus erythematosus Interpregnancy interval > 10 years Thrombophilia BMI at first visit > 35 kg/m2

Chronic renal disease Nulliparity Diabetes mellitus Age > 40 years

*Risk factors for preeclampsia by ACOG and NICE recommendations.*

Conception by in vitro fertilization

Preeclampsia develops only as a complication of pregnancy. Risk factors are presented in **Table 2** together with data of increased risk for some items [15].

The role of biomarkers in preeclampsia diagnosis is becoming increasingly important. A literature review gives us a range of biomarkers that have proved to be sufficiently specific and sensitive to be classified as potential biomarkers (**Figure 3**). The most researched with data on specificity and sensitivity are given in **Table 3**. A good biomarker would be one, which may have the potential of identifying women earlier in their disease course. There have been also many studies investigating

*Biochemical markers in preeclampsia. sFlt-1, soluble fms-like tyrosine kinase 1; PlGF, placental growth factor; sEng, soluble endoglin; PP13, placental protein 13; PAPP-A, pregnancy-associated plasma protein A.*

should be advised to take aspirin from 12 weeks gestation [16].

multiple-marker algorithms for predicting preeclampsia.

**6. Biochemical markers**

*preeclampsia*

**Table 2.**

The National Institute for Health and Care Excellence (NICE) recommends that women with high and more than one of the moderate risk factors for preeclampsia

Chronic hypertension

*ACOG, American College of Obstetricians and Gynecologists; NICE, National Institute of Clinical Excellence; PE,* 

**ACOG recommendation, any risk factor [1] NICE guidelines, one high risk or two moderate risk factors [15]**

**64**

**Figure 3.**

*Biomarker test characteristics for prediction.*
