*7.1.2 Second phase: systemic endothelial dysfunction*

As previously mentioned, systemic endothelial dysfunction in these patients may explain all or almost all of the clinical signs, such as hypertension, proteinuria, or abnormalities in target organs such as the liver, the central nervous system, or the kidneys.

Among the various findings upholding this theory, we can mention the following:


An important factor for future consideration is that the increased concentrations of sFlt-1 generally precede, by 5 weeks, the development of clinical manifestations and appear to be most elevated in the initial phase of severe preeclampsia. However, neither PlGF nor VEGF, measured during gestation, appears to decrease prior to the onset of preeclampsia symptoms.

Most recently, decreases in urinary PIGF have been described before the development of preeclampsia. Some authors have speculated that sFlt-1 plays a beneficial role in fetal circulation and that preeclampsia is a reflection of a maladaptive effect of its release into the maternal circulation. Thus, in the setting of some spiral arterioles with increased resistance, vasoconstriction of the nonplacental maternal circulation would theoretically increase the cardiac output percentage reaching the

placental sub-circulation. Although most cases of preeclampsia are sporadic, some authors suggest that genetics play a role in the development of this entity based on a series of findings:


#### **7.2 Preeclampsia-eclampsia in adolescents**

Traditional references accept that the risk of preeclampsia-eclampsia in adolescents is twice that in the adult population. However, literature reviews are contradictory; while one group of authors refer to an increased risk of preeclampsia in adolescents [21], others detect no differences between these and adult pregnant women, as shown in **Table 2**.

Several studies and meta-analysis [22] detect a significant difference between pregnant adolescents and adult women, with up to 20% more preeclampsia events in pregnant adolescents than in adult women [23]; they actually report a greater risk of preeclampsia-eclapmsia in the group of adolescents between the ages of 13 and 16 when compared with women between the ages of 20 and 34, OR 2.97 (95%CI 1.62–5.42) [24], as well as lower frequencies of preeclampsia in adolescents (5%) vs. 1.5% in the adult group, and the difference was statistically significant, OR 3.66 (95%CI 1.67–7.72) [25].

Therefore, the frequency of preeclampsia in adolescents is currently different according to the studied population as a result of many factors such as prenatal care and body weight changes in pregnancy [26–29].

There is significant bias in observational studies that depend on the type of design and case identification; in these cases, no significant association is found suggesting an increased frequency of preeclampsia in pregnant adolescents, RR 0.88 (95%CI 95% 0.73–1.23). On the contrary, if we take into account follow-up studies, the pregnant adolescent is 23% less likely to develop preeclampsia when compared with pregnant women in other age ranges, RR 0.77 (95%CI 0.64–0.92).

Therefore, the available evidence suggests that adolescence is not a determining factor in the development of preeclampsia and eclampsia, but geographic area does appear to be an additional factor.

In a systematic review [30] describing pregnant adolescents that participated in integral prenatal care programs, they had a lower risk of developing pregnancyinduced hypertension (RR 0.59) than those following traditional prenatal care programs. This means that integral prenatal care programs focused on adolescents decrease the frequency of pregnancy-induced pregnancy by 41% [10].

Due to the heterogeneous presentations of preeclampsia in adolescents from different regions, age is probably not a determining factor but is rather associated to

**133**

**Table 2.**

*Adolescence and Preeclampsia*

*DOI: http://dx.doi.org/10.5772/intechopen.86147*

Bostanci et al. [21] Age of

Early adolescent 11–13 years

> Middle adolescent 14–16 years

Late adolescent 17–19 years

inadequate prenatal care, among others.

*Prevalences of preeclampsia in adolescents.*

leading to nutritional deficiencies [31].

other variables, such as excess weight, excessive weight gain during pregnancy, and

Parra [38] Under 19 year 13.5% The prevalence is greater than 17–19

Zeck et al. [25] 5% in adolescents vs 1.5% in adults OR 3.666 (1.627, 7.723) Tebeu et al. [24] Risk of 13–16 vs 20–34 years OR 2.974 (1.627, 5.427) Gronvik [22] Meta-analysis OR 3.52 (2.26, 5.48)

> resolution P < 0.001

Garmer [39] Hypertensive disorders related with pregnancy P = 0.99

Azevedo et al. [6] Hypertensive disorders in pregnancy 10%

37 weeks 4.78

years before the age of 17 p < 0.001

Prevalence of preeclampsia P < 0.001

aOR p < 0.001

(0.031, 0.63)

(0.31, 0.63)

(1.51, 3.01)

Number of appointments P < 0.001

Adult 5.9% 2.1

<20 years 20–34 years 8.7% 9.2%

36 weeks 3.0 4.8% 1.14

38 weeks 5.54 2.7% 0.44

Two factors warrant analysis in terms of the development of preeclampsia in pregnant adolescents; the first is its association with obesity. Obesity is currently considered an epidemic in which one of every four women in reproductive age is obese and over half of women between the ages of 20 and 39 have excess weight or obesity. Obesity has been reported to increase the risk of adverse maternofetal outcomes due to its association to and development of comorbidities such as gestational diabetes, fetal macrosomia, an increase in cesarean sections, and preeclampsia. Its genesis is the increase in oxidative stress; an increase in circulating pro-inflammatory biomarkers such as C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and interleukin-8; the presence of dyslipidemia, insulin resistance, and abnormalities of endothelial function, all playing a role in the pathogenesis of preeclampsia [31]. Another factor leading to a poor maternal-perinatal outcome and that also increases the risk of preeclampsia is an inadequate nutrient intake, including calcium, zinc, vitamin C, vitamin E, and essential fatty acids. This factor has a doubly negative effect and results from the fact that adolescents are still growing, and during pregnancy, nutrients compete with the fetus for development, therefore

As to the studies recommended in pregnant adolescents to screen for preeclampsia, there are currently no specific tests that can help establish a preclinical diagno-

1.First trimester combined test: markers (weight, blood pressure), ultrasound markers (uterine Doppler), and biochemical markers (PAPP-A, sFlt-1/PIGF).

sis, so the methods used in the general population are the only option:


#### **Table 2.**

*Prediction of Maternal and Fetal Syndrome of Preeclampsia*

series of findings:

without this history.

women, as shown in **Table 2**.

(95%CI 1.67–7.72) [25].

appear to be an additional factor.

development of the disease.

the previous partner was normotensive [20].

**7.2 Preeclampsia-eclampsia in adolescents**

and body weight changes in pregnancy [26–29].

placental sub-circulation. Although most cases of preeclampsia are sporadic, some authors suggest that genetics play a role in the development of this entity based on a

• Primiparous women with a positive family history of preeclampsia have a twoto fivefold greater risk of developing preeclampsia than primiparous women

• Studies in women pregnant with males that were the result of a gestation with preeclampsia have greater probabilities of developing the disease in their pregnancies.

• In sisters with preeclampsia, the genetic imprint plays a major role in the

• Women who became pregnant with men whose previous partner had preeclampsia have greater probabilities of developing the disease if gestation with

Traditional references accept that the risk of preeclampsia-eclampsia in adolescents is twice that in the adult population. However, literature reviews are contradictory; while one group of authors refer to an increased risk of preeclampsia in adolescents [21], others detect no differences between these and adult pregnant

Several studies and meta-analysis [22] detect a significant difference between pregnant adolescents and adult women, with up to 20% more preeclampsia events in pregnant adolescents than in adult women [23]; they actually report a greater risk of preeclampsia-eclapmsia in the group of adolescents between the ages of 13 and 16 when compared with women between the ages of 20 and 34, OR 2.97 (95%CI 1.62–5.42) [24], as well as lower frequencies of preeclampsia in adolescents (5%) vs. 1.5% in the adult group, and the difference was statistically significant, OR 3.66

Therefore, the frequency of preeclampsia in adolescents is currently different according to the studied population as a result of many factors such as prenatal care

There is significant bias in observational studies that depend on the type of design and case identification; in these cases, no significant association is found suggesting an increased frequency of preeclampsia in pregnant adolescents, RR 0.88 (95%CI 95% 0.73–1.23). On the contrary, if we take into account follow-up studies, the pregnant adolescent is 23% less likely to develop preeclampsia when compared with pregnant women in other age ranges, RR 0.77 (95%CI 0.64–0.92). Therefore, the available evidence suggests that adolescence is not a determining factor in the development of preeclampsia and eclampsia, but geographic area does

In a systematic review [30] describing pregnant adolescents that participated in integral prenatal care programs, they had a lower risk of developing pregnancyinduced hypertension (RR 0.59) than those following traditional prenatal care programs. This means that integral prenatal care programs focused on adolescents

Due to the heterogeneous presentations of preeclampsia in adolescents from different regions, age is probably not a determining factor but is rather associated to

decrease the frequency of pregnancy-induced pregnancy by 41% [10].

**132**

*Prevalences of preeclampsia in adolescents.*

other variables, such as excess weight, excessive weight gain during pregnancy, and inadequate prenatal care, among others.

Two factors warrant analysis in terms of the development of preeclampsia in pregnant adolescents; the first is its association with obesity. Obesity is currently considered an epidemic in which one of every four women in reproductive age is obese and over half of women between the ages of 20 and 39 have excess weight or obesity. Obesity has been reported to increase the risk of adverse maternofetal outcomes due to its association to and development of comorbidities such as gestational diabetes, fetal macrosomia, an increase in cesarean sections, and preeclampsia. Its genesis is the increase in oxidative stress; an increase in circulating pro-inflammatory biomarkers such as C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and interleukin-8; the presence of dyslipidemia, insulin resistance, and abnormalities of endothelial function, all playing a role in the pathogenesis of preeclampsia [31].

Another factor leading to a poor maternal-perinatal outcome and that also increases the risk of preeclampsia is an inadequate nutrient intake, including calcium, zinc, vitamin C, vitamin E, and essential fatty acids. This factor has a doubly negative effect and results from the fact that adolescents are still growing, and during pregnancy, nutrients compete with the fetus for development, therefore leading to nutritional deficiencies [31].

As to the studies recommended in pregnant adolescents to screen for preeclampsia, there are currently no specific tests that can help establish a preclinical diagnosis, so the methods used in the general population are the only option:

1.First trimester combined test: markers (weight, blood pressure), ultrasound markers (uterine Doppler), and biochemical markers (PAPP-A, sFlt-1/PIGF).


Since there is no defined pattern in adolescent preeclampsia, its diagnosis and treatment must be the same as in the general population.

Therefore, the following recommendations have been established [32]:

In pregnant adolescents, screening, diagnostic, and therapeutic interventions should be similar to those applied in the rest of the population. **Level of evidence, moderate. Recommendation, strong.**

Care of pregnant adolescents must be provided in *ex profeso* clinics with complete, integral, and multidisciplinary programs to decrease maternal and perinatal risks, including pregnancy-induced hypertension. **Level of evidence, moderate. Recommendation, strong.**

Although there is no evidence on the beneficial effect of interventions used to curb weight gain during pregnancy, offering a medical evaluation and nutritional counseling is a good practice to recommend. **Level of evidence, low. Recommendation, strong.**

Every adolescent clinic must establish the incidence of preeclampsia and eclampsia in its patient population and determine which factors are associated to their development. **Level of evidence, low. Recommendation, strong.**

According to the diagnostic situation of preeclampsia and eclampsia in each adolescent clinic, screening, preventive, early detection, and therapeutic programs must be designed. **Level of evidence, moderate. Recommendation, strong.**

In adolescents with preeclampsia, the disease is generally manifested in the latter part of gestation, close to full-term delivery, so good prenatal care fosters a timely diagnosis of hypertensive disease in earlier stages and improves maternal and fetal outcomes. In the case of the induction of delivery, outcomes will also be improved by decreasing the need for cesarean delivery even in the cases of severe preeclampsia: the neonatal outcome also improves since age is not an influencing factor but disease severity is.
