Preeclampsia: Effect on the Fetus and Newborn

Ligia Maria Suppo de Souza Rugolo, Maria Regina Bentlin and Cleide Enoir Petean
Trindade
NeoReviews 2011;12;e198-e206
DOI: 10.1542/neo.12-4-e198

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Article

cardiovascular

Preeclampsia: Effect on the Fetus and Newborn

Ligia Maria Suppo
de Souza Rugolo, MD,*

Abstract

Maria Regina Bentlin,

Preeclampsia (PE) is the most common medical complication in pregnancy and a major
cause of maternal and fetal morbidity and mortality. This disease is a great challenge for
obstetricians because there are no effective interventions to treat or prevent it, and
antenatal care involves a difficult balance between the risks for women to continue
pregnancy and the risks for the babys early birth. Fetal complications in PE are directly
related to gestational age and the severity of maternal disease and include increased rates
of preterm delivery, intrauterine growth restriction, placental abruption, and perinatal
death. The major complications for the newborn are related to prematurity, although the
data on the morbidity and outcome for preterm infants of women who have PE are
conflicting, and few studies address this issue. The pathogenesis of PE involves abnormal
placentation associated with immune and vascular events that result in endothelial dysfunction and clinical manifestations of PE. This disease has been associated with imbalance
in angiogenic factors and oxidative stress. Nevertheless, only a limited number of studies
have been carried out on fetuses and newborns that suggest that infants born from women
who have PE are exposed to increased oxidative stress. Because oxidative stress and free
radicals may play roles in several neonatal diseases, a direct effect of maternal disease on
neonatal outcome is expected, and further research on such neonates, in the short- and
long-term, is urgently needed.

MD,* Cleide Enoir Petean

Trindade, MD*

Author Disclosure
Drs Suppo de Souza
Rugolo, Bentlin, and
Trindade have
disclosed no financial
relationships relevant
to this article. This
commentary does not
contain a discussion
of an unapproved/
investigative use of a
commercial product/

Objectives

device.

1.
2.
3.
4.

After completing this article, readers should be able to:

Recognize the importance of PE.

Understand the pathophysiology of the disease and its related fetal effects.
Describe the most common fetal complications in PE.
Characterize the newborn whose mother has PE.

Incidence, Definition, and Risk Factors

Hypertensive disorders are the most common medical complications in pregnancy and
major causes of maternal, fetal, and neonatal morbidity and
mortality. Rather than clarify all the complex pathophysiology
of PE, this article discusses some aspects that can help neonaAbbreviations
tologists understand the effects of the disease on the fetus and
the newborn.
IUGR:
intrauterine growth restriction
PE is a great challenge to obstetricians because its cause is
MDA:
malondialdehyde
unknown,
its pathophysiology is complex and incompletely
NHBPEP: National High Blood Pressure Education
understood,
its diagnosis may be difficult to determine, there
Program
are
no
effective
treatments, and antenatal care involves a diffiNO:
nitric oxide
cult
balance
between
the risks for women to continue pregPE:
preeclampsia
nancy
and
those
for
the
babys early birth.
PIGF:
placental growth factor
The
disease
can
lead
to
many acute maternal complications,
sEng:
soluble endoglin
such
as
progression
to
eclampsia,
acute renal or hepatic failure,
sFlt1:
tyrosine kinase
pulmonary
edema,
and
the
HELLP
syndrome (hemolysis,
SGA:
small for gestational age
elevated
levels
of
liver
enzymes,
and
low
platelet count). FurTGF:
transforming growth factor
thermore,
there
is
increased
risk
for
long-term
cardiovascular
VEGF:
vascular endothelial growth factor
disease. (1)(2)(3)
*Botucatu School of Medicine University Hospital, Sao Paulo State University (UNESP); Division of Neonatology, Department of
Pediatrics, Botucatu, Sao Paulo, Brazil.
e198 NeoReviews Vol.12 No.4 April 2011

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cardiovascular

The incidence of PE is about 5% to 10% of all pregnancies, with higher rates reported in first pregnancies,
twin pregnancies, and in women who have had previous
PE. Fifty percent of hypertensive disorders of pregnancy
are defined as PE, the most important manifestation of
the disease. (2)(4)(5) Among the several risk factors for
PE are twin pregnancies, primiparity, previous PE, pregestational diabetes mellitus, chronic hypertension, and
obesity. A family history of PE increases the womens risk,
suggesting a possible genetic predisposition. (1)(3)(6)
The most widely accepted definition and classification
of hypertensive disorders of pregnancy was proposed by
the National High Blood Pressure Education Program
(NHBPEP) Working Group on High Blood Pressure in
Pregnancy, which used a blood pressure of 140/90 mm
Hg or higher on two separate occasions at least 4 hours
apart as the diagnostic criterion for hypertension. (7) The
NHBPEP defined four hypertension categories in pregnancy: chronic hypertension, gestational hypertension,
PE, and PE superimposed on chronic hypertension
(Table 1) (Fig. 1).
PE is characterized as severe according to hypertension degree (arterial pressure 160/110 mm Hg on two
occasions 6 hours apart); proteinuria (5 g/24 hours
or 3 in two urine samples); or any of the following:
cerebral/visual disturbances, abdominal pain, abnormal
liver function, oliguria, pulmonary edema, thrombocytopenia, or fetal growth restriction. (1)

ing cytokines, which promote the infiltration of spiral

arteries by trophoblasts, thus causing a decidual inflammatory response. (1) (8) In this case, normal pregnancy
has been viewed as a state of mild inflammation, and PE
is associated with an intense systemic inflammatory response related to endothelial cell dysfunction and leukocyte activation. (9)
PE is considered a two-stage disease (Fig. 2) that
begins with poor placentation and reduced uteroplacental blood supply, resulting in placental hypoxia. This
first stage, with silent placental events, is followed by the
release of several mediators: growth factors and their
soluble receptors, inflammatory cytokines, placental debris, and products of placental oxidative stress. Such
mediators cause endothelial cell dysfunction and the
systemic inflammatory syndrome, leading to the clinical
manifestation of PE (second stage). (9)
The existence of two PE subsets of early and late
disease that have different biochemical and clinical features was supported in a mouse model. The model
showed marked pathologic changes in placentas, lower
fetal survival, and more severe intrauterine growth restriction (IUGR) in early PE but no significant changes
in placental and fetal growth in late PE, thus suggesting
that early PE is a placental disease and late PE is a
maternal systemic disease. (10) This finding could explain the poor outcome of fetuses and infants whose
mothers develop early PE.

Pathophysiology
Although the cause of PE remains unknown, there are no
doubts that the placenta is a triggering organ in development of the disease. Immune and vascular events have
been implicated in the pathogenesis.

The Role of the Immune System

The innate/inflammatory response plays an important
role during placentation, with natural killer cells secretTable 1.

preeclampsia

The Role of Oxidative Stress

Oxidative stress results from an imbalance between the
increased generation of reactive oxygen species, including free radicals and the intermediates derived from
the mitochondrial metabolism, and deficiency in antioxidant defense mechanisms. (11)
Placental oxidative stress is regarded as an intermediate
event in the pathogenesis of PE, and although its cause

Classification of Hypertensive Disorders of Pregnancy

Category

Diagnostic Criteria

Chronic hypertension

Hypertension manifested before pregnancy, before 20 weeks of gestation,

or persisting more than 12 weeks postpartum.
Hypertension manifested after 20 weeks of gestation.
Development of hypertension after 20 weeks of gestation, associated
with proteinuria (>0.3 g in a 24-hour urine specimen or >1 on
dipstick in two urine samples) in previously normotensive women.
Preeclampsia diagnosed in previously hypertensive women.

Gestational hypertension
Preeclampsia
Preeclampsia superimposed on
chronic hypertension

From National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy 2000.

NeoReviews Vol.12 No.4 April 2011 e199

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cardiovascular

preeclampsia

signaling cascades, and secretion of

soluble factors, which can subsequently activate the maternal inflammatory response. (13) Evidence that
oxidative stress contributes to endothelial dysfunction, leading to PE, is
supported by a number of reports
showing increased concentrations of
oxidative stress markers (usually malondialdehyde, a major breakdown
product split off from lipid peroxides) in contrast with decreased antioxidant concentrations in maternal
circulation and placentas of women
who have PE. (14)(15)(16)
Nitric oxide (NO) dysfunction is
another pathway involved in the
pathogenesis of PE. NO is a major
vasodilator, synthesized by endotheFigure 1. Incidence and classification of hypertensive disorders in pregnancy. Data from lial cells from L-arginine. EndotheRoberts, et al. (4)
lial dysfunction is characterized by
decreased bioavailability of NO
remains unclear, there is strong evidence that the triggering
through reduced production or increased consumption
event is abnormal placentation with underperfusion, sugby oxidative stress because NO is a highly reactive free
gesting that increased oxidative stress could be generated in
radical. Endothelial cells can also produce methylated
the placenta through the hypoxia-reperfusion mechanism.
amino acids, such as asymmetric dimethylarginine, an
(12) Oxidative stress promotes lipid peroxidation in placenendogenous competitive inhibitor of NO synthase,
tal cell membranes and can lead to endothelial cell dysfuncwhich has been found to be increased in women at risk
tion through increased production of thromboxane A2,
for PE or IUGR. (13)(17) Decreased concentrations of
release of toxic products or activation of several intracellular
NO in plasma and the placenta have been found in
women who have PE, and although
its role in the pathophysiology of
PE has not been well defined, it is
postulated that low NO concentrations might contribute through a
lack of paracrine vasodilatory effect
on the uteroplacental blood flow.
(12)(18)
The pathogenic pathway of increased oxidative stress associated
with deficient antioxidant defenses
in PE is of great clinical relevance
and has resulted in preventive supplementation strategies with vitamin antioxidants among pregnant
women at high risk for PE. However, randomized, controlled supplementation trials with vitamins C
Figure 2. Pathogenesis of preeclampsia. IFNinterferon, IUGRintrauterine growth and E did not demonstrate benefirestriction, NKnatural killer, PEpreeclampsia, ROSreactive oxygen species, TGF cial effects in the prevention of PE
transforming growth factor
and low birthweight, even in popue200 NeoReviews Vol.12 No.4 April 2011

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cardiovascular

lations that had low nutritional status from developing

countries. (19) Possible explanations include inappropriate start time, vitamin dose, and spectrum to target
oxidative stress. Further, oxidative stress may be a pathway in the pathogenesis and not the cause of PE.
Among antioxidants, glutathione peroxidase plays a
critical role in the control of lipid peroxidation, and
recent studies have reported significant reductions in
maternal plasma and placental glutathione peroxidase
activities in women who have PE. (16)(20)
In general, studies on oxidative stress-related complications in pregnancy have focused on maternal parameters. Although a limited number of studies have been
carried out on fetal oxidative status and umbilical cord
blood, the results have consistently shown an upregulation of oxidative stress markers and altered antioxidant
status in fetal circulation. These data suggest that the
fetus is affected by oxidative stress in PE and raise concern about fetal and neonatal outcomes. (14)(16)(21)
Ongoing research by our group at Sao Paulo State
University aims to evaluate the role of oxidative stress on
the neonatal outcomes of preterm infants born to
women who have PE. Interesting preliminary results
have been obtained. A prospective case-control study
involved 30 preterm infants (34 weeks of gestation)
born to women who had PE and 30 gestational agematched preterm babies born to normotensive mothers.
The mean gestational age was 30 weeks. Glutathione,
glutathione peroxidase, glutathione reductase, malondialdehyde (MDA), and NO were measured simultaneously in placental tissue, umbilical venous cord blood,
and neonatal peripheral blood samples on the fourth day
after birth. The same determinations were made in spot
urine samples collected at postnatal days 1 and 4. The
outcomes of interest included the incidences of respiratory distress syndrome, intraventricular hemorrhage,
periventricular leukomalacia, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity,
and death during hospitalization. There were no differences in neonatal morbidity and mortality between the
two groups. Oxidative stress changes were not found in
the placenta, but they were detected in the umbilical
venous blood and in urine on the first and fourth days
after birth. Umbilical cord concentrations of glutathione
and urinary concentrations of MDA correlated with neonatal outcomes. These results show that preterm infants
of women who have PE are exposed to increased oxidative stress during the first days after birth, and despite no
immediate clinical manifestation, the long-term outcomes are yet to be determined.

preeclampsia

The Role of Angiogenic Factors

Placental angiogenesis is biphasic, with endothelial proliferation at mid-gestation and vascular remodeling in the
second half of pregnancy. It is regulated by many growth
factors, but vascular endothelial growth factor (VEGF)
signaling represents a critical rate-limiting step. The placental growth factor (PIGF) is a member of the VEGF
family, released by activated endothelial cells, which enhances the VEGF response. (22)
Expressed in endothelial cells, endoglin functions as a
coreceptor for transforming growth factor (TGF)-,
which modulates its effects on angiogenesis. The soluble
form of endoglin (sEng) has an antiangiogenic effect,
inhibiting the TGF- signaling pathway, and soluble
forms, such as tyrosine kinase (sFlt1), are natural antagonists of VEGF-A and PIGF. Both of these antiangiogenic factors are increased in PE and correlate with
complications, including placental abruption, IUGR,
and early PE onset. sEng causes increased vascular permeability and hypertension, and its effects can be amplified by sFlt1. (22)(23) Experimental in vitro and human studies have suggested that an imbalance in
angiogenic/antiangiogenic factors, represented by high
concentrations of sFlt1 and sEng with low concentrations of PIGF and VEGF, causes endothelial cell dysfunction and is associated with PE development. (3) The
precise mechanisms by which angiogenic factors participate in PE are not clear. Placental hypoxia has been
considered to be the primary stimulus to sFlt1 release,
although inflammatory mechanisms may also contribute. (23)
Increasing evidence suggests an important role for
angiogenic factors on the pathophysiology of PE. A
different profile in angiogenic/antiangiogenic balance
may determine pregnancy outcome: PE or IUGR. In
a case-control study, investigators demonstrated that
changes in the proangiogenic factor (PIGF) and in antiangiogenic factors (sEng, sVEGFR-1) occur before
PE development, with significant increases in antiangiogenic factors in the second trimester. Patients who had
small-for-gestational-age (SGA) neonates showed no
change in sVEGFR-1 but a higher concentration of
sEng from the first trimester onward, suggesting a
chronic antiangiogenic state that predisposes to SGA
delivery. (22)
Currently, angiogenic factors are the most promising
PE biomarkers and will continue being of utmost importance because they could allow early diagnosis, better
management, and proper intervention. (3)
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cardiovascular

preeclampsia

Genetics
Recently, epigenetic features, such as imprinting, and a
growing number of genes have been implicated in the
pathogenesis of PE, although the results are still not
clear. Progress in this area should enhance the understanding of this disease by helping to identify new diagnostic biomarkers and propose preventive interventions.
(1)(24)

New Information
New insights into the pathophysiology of PE have arisen
from recent experimental studies using more reliable
models and newer technologies. In a rat model of placental insufficiency using real-time polymerase chain reaction, a disturbed regulation in the expression of genes
involved in blood pressure, angiogenesis, and immune
cell regulation as well as an overexpression of genes
related to the renin-angiotensin system were found, suggesting a role for this system in the pathogenesis of
placental insufficiency. (24)

Obstetric Management
Despite some disagreement about obstetric monitoring
and management of PE, there is no question that adequate prenatal care is the most important factor for early
diagnosis and safe management of mothers and fetuses.
Women in whom PE develops at or near term usually
have mild disease and a favorable gestational outcome. In
these cases, labor induction is effective and safe to prevent maternal complications. (25)(26)
The management of pregnancies that involve early
severe PE is an issue of concern and debate between
obstetricians and neonatologists because expectant management can positively affect perinatal outcome but may
not be safe for the mother. A randomized, controlled
trial addressing this issue (27) showed that expectant
management of severe PE before 34 weeks of gestation
improves neonatal outcome by delaying delivery by 1 to
2 weeks and reducing neonatal complications without
increasing the risk for maternal complications. A systematic review assessing interventionist versus expectant care
for PE before 34 weeks of pregnancy included only two
randomized, controlled trials, and the data were insufficient for reliable conclusions about the best intervention.
In the interventionist group, the risk for respiratory
distress syndrome, necrotizing enterocolitis, and neonatal intensive care unit admission was higher, although
babies were less likely to be SGA. (28)
As recently proposed by Colleta and Simpson, (26)
e202 NeoReviews Vol.12 No.4 April 2011

PE management depends on gestational age, fetal status,

and severity of maternal disease (Table 2).

Perinatal Outcome
The major issues are high perinatal mortality rates,
IUGR, and increased neonatal morbidity due to preterm
delivery. (4)(29) Uteroplacental insufficiency, placental
abruption, and low gestational age are considered the
primary factors associated with a poor perinatal outcome.
(29) In addition, the influence of maternal disease severity, such as degree of hypertension, increased proteinuria, or the presence of HELLP syndrome, on perinatal
outcome has been emphasized. (27)(30) It is noteworthy that the perinatal outcome should be modulated
by the obstetric management of severe PE.
Severe proteinuria has been associated with the early
onset of PE and early gestational age at delivery, with
subsequent neonatal prematurity complications, although it does not seem to be an independent marker of
adverse perinatal outcome. (27) The HELLP syndrome
is associated with increased maternal mortality and morbidity; high perinatal mortality rates (200 to 400 in
1,000); and increased incidences of placental abruption,
fetal distress, and IUGR. Prompt delivery is usually recommended. (30)

Mortality
Perinatal mortality rates range from 59 in 1,000 in developed countries to more than 300 in 1,000 in lowincome countries, and they are influenced by viability
thresholds. (2) Rates greater than 200 in 1,000 are
usually reported in early severe PE at 24 to 34 weeks of
gestation, and extremely high rates of more than 800 in
1,000 are seen with severe PE at 24 or fewer weeks of
gestation (Fig. 3). Perinatal mortality is increased in
infants affected by IUGR or asphyxia. (27)(31)
Current stillbirth rates in PE range between 9 and
51 in 1,000 births. Women with PE superimposed on
chronic hypertension are 4.4 times more likely to have a
stillbirth. (26)

IUGR
Fetal growth restriction is the issue of most concern.
Although the relationship between IUGR and PE has
been controversial, a high incidence of SGA infants in
women who have PE has been reported, ranging from
15% to more than 50%. (4)(32) A retrospective cohort
study showed that about 15% of pregnancies affected by
IUGR later developed PE. (33) An analysis of a large
database from the World Health Organization investigated whether PE, gestational hypertension, and IUGR

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cardiovascular

Table 2.

preeclampsia

Management of Preeclampsia

Severity of Disease

Gestational Age

Management

Mild

Any

Severe

<24 weeks
24 to 34 weeks

Control for severe disease and fetal growth

Consider delivery at 37 weeks gestation
Delivery
Administer corticosteroids for fetal lung maturation
Administer antihypertensives, magnesium sulfate
Consider delivery if there is maternal or fetal risk
Delivery

>34 weeks

are related conditions. (5) PE and gestational hypertension groups had similar risk factors and neonatal
outcomes. However, risk factors differed for PE and
IUGR, and although both diseases increased fetal and
neonatal mortality and prolonged neonatal intensive care
unit stay, only PE increased the risk for preterm delivery.
The authors concluded that PE and IUGR appear to be
independent entities.
The relationship between IUGR and PE severity as
well the possible confounding effect of chronic hypertension on the risks for IUGR in PE was investigated in a
well-designed prospective case-control study. (34) The
prevalence of chronic hypertension was 16% and 5% in
the PE and control groups, respectively. Women who
had PE had an increased risk for IUGR, especially those
who did not have chronic hypertension. Among patients
who had chronic hypertension, PE development did not
affect the risk for IUGR, suggesting different pathways
of fetal growth impairment. There was moderately increased risk for IUGR among severe cases compared with
mild cases of PE. These findings emphasize that PE is
independently associated with IUGR, but they could not
confirm the value of IUGR in the diagnostic criteria of
severe PE.

New Information
An interesting finding that contributed to the understanding of PE- and IUGR-related mechanisms was recently reported by Soto and associates. (35) The authors
focused on complement system activation because it has
been associated with vascular injury, growth restriction,
and fetal death. Complement activation generates split
products (C3a, C4a, C5a) that have proinflammatory
properties, leading to increased vascular permeability,
smooth muscle contraction, and chemotaxis of inflammatory cells. The aim of the study was to determine the
profile of maternal complement split products in women
who had SGA pregnancies, PE, and PE with SGA pregnancies. Higher C5a concentrations were found in PE
(with or without SGA) compared with SGA pregnancies,
suggesting that C5a participates in leukocyte activation
and inflammation. This finding reinforces the role played
by the innate immune system in the pathogenesis of PE,
but complement activation was not observed in women
who had SGA pregnancies. These results showed that PE
and SGA pregnancies have different profiles: PE is a
systemic maternal disease that can be associated with fetal
growth restriction; SGA pregnancy is primarily a fetal
disease.

Prematurity

Figure 3. Perinatal mortality in preeclampsia according to

gestational age. Data from Haddad and Sibai. (27)

Epidemiologic studies have reported alarmingly high

rates of preterm births, predominantly due to increasing
indications for preterm delivery, and PE is one of the
most common of these indications. (1)(2)(4) Prematurity per se has a major impact on neonatal mortality and
morbidity, but preterm newborns of women who have
PE are of great concern because strong evidence shows
that they are exposed to increased oxidative stress, which
has been implicated in the pathogenesis of serious diseases in neonates. (11) Thus, an unfavorable outcome
could be expected in infants of women who have PE. (2)
(4)(32) However, reports of the early neonatal outNeoReviews Vol.12 No.4 April 2011 e203

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cardiovascular

Table 3.

preeclampsia

Neonatal Complications in Pregnancies Involving Preeclampsia

Problem

Comments

Respiratory distress syndrome

Thrombocytopenia

No difference in incidence; lung maturity is not accelerated in PE. (36)(37)

Associated with low birthweight and prematurity; early manifestation and
transient course. (38)
High incidence in the first 72 hours after birth and may be associated with
increased risk of infection. (39)(40)
Increased risk, primarily newborns who have intrauterine growth restriction. (41)
Increased neonatal encephalopathy in term neonates. (42)
No difference or decreased incidence of IVH and PVL in preterm infants. (43)(44)
Neuroprotective effect of magnesium sulfate. (45)

Neutropenia
Necrotizing enterocolitis
Intraventricular hemorrhage/
periventricular leukomalacia
(IVH/PVL)

come in infants of hypertensive mothers are conflicting

(Table 3). In addition, PE may have long-term consequences for preterm and SGA infants. (2)(29)(46)
It is still unclear whether preterm infants born to
women who have PE have worse outcomes than those
delivered preterm for other causes. It is also unclear whether
the increased adverse perinatal outcome in these infants
is due to shorter gestation or if there is a direct effect of
maternal disease or treatment on the fetus and newborn.
This is a very important line of investigation, considering
the multiple mediators involved in the pathogenesis of
PE. Further research is needed for better characterization
of infants of women who have PE and to aid in predicting
risks in their neonatal and later outcome.

Conclusion
PE remains a major obstetric problem because it is typically an unpredictable maternal disease with variable
degrees of fetal involvement. Progress has been made in
understanding the complex immunologic, vascular, and
genetic factors involved in the pathophysiology of the
disease, but to date, such progress has not been translated into clinical practice. No significant improvement
has been observed in pregnancy and perinatal outcomes.
PE remains an important cause of maternal and fetal morbidity and mortality. Early severe PE and IUGR deserve
special attention from obstetricians and neonatologists.

American Board of Pediatrics Neonatal-Perinatal

Medicine Content Specifications
Know the effects on the fetus and/or
newborn infant of mild preeclampsia and
its management.
Know the effects on the fetus and/or
newborn infant of severe preeclampsia,
including HELLP syndrome, and its management.

e204 NeoReviews Vol.12 No.4 April 2011

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cardiovascular

preeclampsia

NeoReviews Quiz
1. A previously healthy 21-year-old primigravid woman carrying a singleton fetus seeks consultation at an
estimated gestational age of 24 weeks. Her blood pressure ranges from 142 to 148 mm Hg (systolic) and
from 92 to 96 mm Hg (diastolic). She is complaining of abdominal pain and has proteinuria (urinary
protein loss >2.5 g/24 hours). Her liver function test results and blood counts are normal. Abdominal
ultrasonography reveals a normal fetus with appropriate growth for gestational age. Of the following, the
most accurate designation for the hypertensive disorder of pregnancy in this woman is:
A.
B.
C.
D.
E.

Chronic hypertension.
Eclampsia.
Gestational hypertension.
HELLP syndrome.
Preeclampsia.

2. Preeclampsia is classified as early or late disease, based on specific clinical, biochemical, and
histopathological characteristics. Of the following, early preeclampsia is believed to be a:
A.
B.
C.
D.
E.

Fetal disease.
Maternal autoimmune disease.
Maternal free radical disease.
Maternal inflammatory disease.
Placental disease.

3. Several biomarkers have been studied in pregnant women to allow for early detection of preeclampsia and
timely intervention. Of the following, the most promising biomarkers for preeclampsia are:
A.
B.
C.
D.
E.

Angiogenic factors.
Complement split products.
Free radicals.
Inflammatory cytokines.
Nitric oxide synthases.

4. The management of preeclampsia, including delivery of the infant, depends on gestational age, fetal status,
and severity of maternal illness. Of the following, the optimal time for delivery in a pregnancy complicated
by mild preeclampsia first observed at 28 weeks gestation is at a gestational age of:
A.
B.
C.
D.
E.

28
31
34
37
40

weeks.
weeks.
weeks.
weeks.
weeks.

5. Preeclampsia has several adverse effects on the perinatal outcome. Of the following, the most common
perinatal complication of preeclampsia is:
A.
B.
C.
D.
E.

Fetal growth restriction.

Maternal cerebrovascular stroke.
Neonatal periventricular leukomalacia.
Neonatal respiratory distress.
Placental abruption.

e206 NeoReviews Vol.12 No.4 April 2011

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Preeclampsia: Effect on the Fetus and Newborn

Ligia Maria Suppo de Souza Rugolo, Maria Regina Bentlin and Cleide Enoir Petean
Trindade
NeoReviews 2011;12;e198-e206
DOI: 10.1542/neo.12-4-e198

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