**2. Preeclampsia**

Hypertensive diseases in pregnancy are the most common causes of mortality and maternal and fetal morbidity (WHO, 2005). PE is a frequent cause for hospitalization, labour induction and dystocic labour, reasons that justify the study of this disease.

Some controversy exists concerning the terminology and the classification of hypertensive disorders; indeed, several reported studies used different classifications. The more consensual, is the classification proposed by the "International Society for the Study of Hypertension in Pregnancy" (ISSHP). The diagnosis of hypertension in pregnancy, according to this classification (Brown et al., 2001) is performed in accordance with the following criteria: an occasional measurement of diastolic blood pressure greater than 110 mmHg, or two or more consecutive measurements equal to or greater than 90 mmHg, with 6 hours or longer intervals between measurements. PE is defined as the onset of hypertension associated with proteinuria after 20 weeks of gestation, in previously normotensive pregnant women (Table 1). Typically, PE is asymptomatic, but in its most severe form it may also present with headache, epigastric pain, visual disturbances and changes in consciousness.

#### **Preeclampsia ISSHP classification:**

Hypertension - diastolic blood pressure ≥ 110 mmHg (an occasional measurement), or ≥ 90 mmHg (two or more consecutive measurements)

Proteinuria (≥ 300 mg/day)

Both present, after 20 weeks of gestation, returning to normal postpartum

Table 1. Preeclampsia ISSHP classification

Eclampsia is the most severe form of pregnancy-induced hypertension. It is characterized by the appearance of seizures, which may occur before, during or within 48 hrs after birth. Eclampsia may appear in pregnant women with moderate increases in blood pressure and mild proteinuria.

#### **2.1 Epidemiology of preeclampsia /risk factors and complications**

PE is a pregnancy specific disorder, characterized by an impaired blood perfusion of vital organs, including the fetal-placental unit. The prevalence of PE, although usually reported as 5 to 8%, presents some variations in the literature (Sibai et al., 2005; Maynard et al., 2008), particularly for different populations.

The risk of developing PE seems to be associated with some factors, such as nulliparity (about 2/3 of cases occur in the first pregnancy), multiple pregnancy, change of paternity, age over 40 years, family history of PE and eclampsia, body mass index (BMI) greater than 35 kg/m2, diabetes, disease prior to pregnancy (e.g., diabetes mellitus, hypertension, renal disease and thrombophilia) and hydatidiform mole (Duckitt & Harrington, 2005; Magnussen et al., 2007; Jim et al., 2010). According to Magnussen et al. (2007), there is an enhanced risk to develop PE, when cardiovascular risk factors, such as increased triglycerides (TG), total cholesterol and LDLc, are present before pregnancy.

Several studies associate smoking habits with a lower risk of developing PE (Magnussen et al., 2007; Wikström et al., 2010). However, maternal smoking is associated with various maternal and fetal complications (Kalle, 2001; Steyn et al., 2006), including placenta previa, low birth weight, preterm birth, miscarriage and neonatal death.

PE is the main maternal risk factor associated with low birth weight newborns and/or IUGR (Table 2). Intrauterine growth restriction and/or fetal death can occur in about 30% of PEc cases as a direct result of placental insufficiency (Jim et al., 2010). The neonatal complications risk is higher in cases of severe PE and eclampsia (Duley, 2009). IUGR is associated with a high rate of perinatal morbidity and mortality (Rizzo & Arduini, 2009).

Several studies indicate that PE is associated with a higher incidence of newborns with low birth weight (Groom et al., 2007; Duley, 2009; Wu et al., 2009). In addition, there's an increased incidence of newborns with low birth weight in pregnant women who developed PE at an earlier stage of pregnancy, compared with those who later developed PE (Xiong & Fraser, 2004; Groom et al., 2007). Prematurity is the leading cause of perinatal morbidity and mortality (Goldenberg et al., 2008) and PE is often associated with preterm delivery (Sibai et al., 2005; Goldenberg et al., 2008; Duley, 2009; Wu et al., 2009). Some neonatal complications resulting from PEc pregnancy are described, and are associated with prematurity, including jaundice, respiratory distress, apnea, seizures, hypoglycaemia and prolonged hospitalization (Duley, 2009; Wu et al., 2009).

#### **Newborn complications:**

270 From Preconception to Postpartum

Disturbances in angiogenic/anti-angiogenic factors, in the lipid profile and an enhanced inflammatory response, in the fetal circulation, may cause a short-term effect, such as endothelial dysfunction. However, the impact of these modifications, that are known cardiovascular risk changes, in the future life of these newborn are still unknown and should be clarified. These neonates and their mothers should deserve, therefore, a closer

Hypertensive diseases in pregnancy are the most common causes of mortality and maternal and fetal morbidity (WHO, 2005). PE is a frequent cause for hospitalization, labour

Some controversy exists concerning the terminology and the classification of hypertensive disorders; indeed, several reported studies used different classifications. The more consensual, is the classification proposed by the "International Society for the Study of Hypertension in Pregnancy" (ISSHP). The diagnosis of hypertension in pregnancy, according to this classification (Brown et al., 2001) is performed in accordance with the following criteria: an occasional measurement of diastolic blood pressure greater than 110 mmHg, or two or more consecutive measurements equal to or greater than 90 mmHg, with 6 hours or longer intervals between measurements. PE is defined as the onset of hypertension associated with proteinuria after 20 weeks of gestation, in previously normotensive pregnant women (Table 1). Typically, PE is asymptomatic, but in its most severe form it may also present with headache, epigastric pain, visual disturbances and

Hypertension - diastolic blood pressure ≥ 110 mmHg (an occasional measurement),

Eclampsia is the most severe form of pregnancy-induced hypertension. It is characterized by the appearance of seizures, which may occur before, during or within 48 hrs after birth. Eclampsia may appear in pregnant women with moderate increases in blood pressure and

PE is a pregnancy specific disorder, characterized by an impaired blood perfusion of vital organs, including the fetal-placental unit. The prevalence of PE, although usually reported as 5 to 8%, presents some variations in the literature (Sibai et al., 2005; Maynard et al., 2008),

Both present, after 20 weeks of gestation, returning to normal postpartum

**2.1 Epidemiology of preeclampsia /risk factors and complications** 

clinical follow-up later in life. This issue will be also addressed in this chapter.

induction and dystocic labour, reasons that justify the study of this disease.

**2. Preeclampsia** 

changes in consciousness.

mild proteinuria.

**Preeclampsia ISSHP classification:** 

Proteinuria (≥ 300 mg/day)

Table 1. Preeclampsia ISSHP classification

particularly for different populations.

or ≥ 90 mmHg (two or more consecutive measurements)

Intrauterine growth restriction (IUGR) Prematurity Neurologic lesions Neonatal death Long term chronic diseases ("fetal programming" or "fetal origins of disease in adult life")

Table 2. Newborn complications in preeclampsia

According to Barker's theory, the origin of some adulthood chronic diseases such as cardiovascular diseases, hypertension and diabetes have their origin in intrauterine life (Barker & Bagby, 2005). This hypothesis, called "fetal programming" or "fetal origins of disease," suggests that the intrauterine environment in which the fetus develops may be the origin of diseases in adult life. Changes that may occur in intrauterine environment and that somehow could disrupt normal development of the fetus can trigger metabolic changes, which may result in the development of long-term disorders (Barker, 2004).

Umbilical Cord Blood Changes in Neonates from a Preeclamptic Pregnancy 273

The placenta seems to play a key role in the pathogenesis of PE, since the clinical symptoms disappear only after placental expulsion. PE seems to develop after a partial failure in the process of placentation, a process that occurs between 6-18 weeks of gestation. In this condition, only some of the spiral arteries of the placental circulation are invaded by trophoblasts. In the myometrial spiral arteries the muscular-elastic layer is not replaced; therefore, vascular resistance is higher and uteroplacental flow is reduced, as compared to what occurs in a normal pregnancy. This decrease in placental perfusion may significantly affect oxygenation, nutrition and fetal development. The reduction in placental perfusion in PE is usually accompanied by a reduction in fetal weight for gestational age (Catarino et al.,

The first observations on this phenomenon have been published for over three decades (Brosens et al., 1972), but several authors have confirmed these observations and attempted to clarify the mechanisms involved (Chaddha et al., 2004; Burton et al., 2009). Doppler fluxometry applied to the uterine arteries allowed the confirmation of the hemodynamic disturbances underlying placental insufficiency, and demonstrated that in PE occurs an increased (circulatory) resistance of placental vascular territory (Papageorghiou & Leslie, 2007; Boukerrou et al., 2009). As changes in placental blood flow are observed in PE before the onset of symptoms (Papageorghiou & Leslie, 2007), uterine artery Doppler, is performed

In PE an acute atherosis in the myometrial spiral arteries may also develop. The acute atherosis is an injury similar to the atherosclerotic lesion, characterized by the presence of fibrin deposits, accumulation of foam cells and infiltration of mononuclear leukocytes. This type of injury leads to a reduction of the arteries lumen, and, thus, to a decrease in placental perfusion, even in the absence of an inadequate placentation (Pijnenborg et al., 2006). The atherosis may progress to acute vascular obstruction of the spiral arteries, reducing blood flow to the placenta and causing placental infarction. In a study involving 400 placentas from PEc women, the vascular lesions in the placenta correlated with the severity of this

Placenta has the ability to synthesize several molecules, including mediators of inflammation and angiogenic factors, whose expression appears to be regulated by oxygen pressure and by the presence of oxidative stress (Rusterholz et al., 2007; Redman & Sargent, 2009). The expression of these molecules appears to be affected in PE; placental hypoxia/reperfusion and placental oxidative stress seems to be involved in this regulation, however, other modulators may contribute to that expression, such as genetic and

Some studies state that PE induces changes in the placental expression of tumor necrosis factor (TNF)-α, increasing this and other pro-inflammatory cytokines (Hung et al., 2004), and interleukin (IL)-6 (Bowen et al., 2005); however, there are conflicting results (Rusterholz

Placenta seems to be the main source of placental growth factor (PlGF) and soluble vascular endothelial growth factor receptor (sVEGFR)-1, during pregnancy. A change in placental function may, therefore, interfere with the synthesis of these angiogenic/anti-angiogenic

early in the second trimester of pregnancy, in order to predict PE.

pathology (Ghidini et al., 1997).

immunological factors.

et al., 2007).

**2.2.1 Maternal syndrome of preeclampsia** 

2008a).

There are studies revealing that children of PEc women present in adolescence, higher blood pressure levels with increased risk of developing hypertension, compared to children of normotensive pregnant women (Vatten et al., 2003; Tenhola et al., 2006, Kajantie et al., 2009). In another study, adolescents with low birth weight also presented blood pressure values higher than adolescents who were born with adequate weight (Covelli et al., 2007).

Low birth weight appears to be associated with an increased risk of developing type 2 Diabetes mellitus(Whincup et al., 2008), cardiovascular disease (Barker & Bagby, 2005) and hypertension (Lenfant, 2008) in adult life. This risk appears to be even greater if, in addition to low birth weight, further develop a marked increase in BMI (Eriksson et al., 2007; Barker et al., 2009). In a recent study, Raghupathy et al. (2010) mentioned that individuals who were underweight at birth and during infancy, followed by a sharp increase in BMI during adolescence, were associated with a reduction in glucose tolerance and development of type 2 Diabetes mellitus.
