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Medical Journal of Obstetrics and Gynecology

Review Article

Special Issue on

Prediction of Preeclampsia

Obesity and Risk of

Preeclampsia
Hiroaki Itoh* and NaohiroKanayama

*Corresponding authors
Hiroaki Itoh, Department of Obstetrics and Gynecology,
Hamamatsu University School of Medicine, 1-20-1
Handayama, Higashi-ku, Hamamatsu 341-3192, Japan,
Phone: +81-53-435-2309; FAX: +81-53-435-2308; E-mail:

Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine,

Japan

Submitted: 25 April 2014

Accepted: 09 June 2014
Published: 10 June 2014

Abstract
The incidence of obesity in women of childbearing age has consistently increased
in the last half-century. Maternal obesity is a strong risk factor that a deteriorates the
perinatal outcome of both mothers and neonates, and this has raised specific issues
related to the management of pregnancy in obese women. Maternal obesity is a
well-known risk factor for the development of preeclampsia. Several large population
studies have shown that obese women are two to three times more likely to develop
preeclampsia than their leaner counterparts. This association between maternal obesity
and an increased incidence of preeclampsia is an important factor that deteriorates
perinatal mortality and morbidity in obese mothers. In this review, we described
the epidemiology, possible mechanistic background, transgenerational effect, and
lifestyle interventions concerning the association between maternal obesity and risk
of preeclampsia.

INTRODUCTION
The global epidemic of obesity is unfolding, resulting in
new challenges for all health-care professionals. Obesity is
often associated with insulin resistance, dyslipidemia, and
hypertension, which has led to the concept of metabolic syndrome
[1,2]. Recent evidence has suggested that the prevention of
obesity may begin before conception [3,4].
The rapid shift in populations towards a more obese
phenotype in a relatively short period of time, less than half
a century, has led to a marked increase in the incidence of
overweight and obese women of childbearing age, which has
raised specific issues for the management of pregnancy in obese
women. The National Health and Nutrition Examination Survey
revealed that more than half of pregnant women are overweight
or obese, and 8% of reproductive-aged women are extremely
obese in United States [5]. Numerous studies have reported
that maternal obesity is associated with an increased risk of
adverse pregnancy outcomes including preeclampsia, gestational
diabetes, infectious morbidity, postpartum haemorrhage, the
delivery of large-for-dates babies, and stillbirth [6-16]. This
review highlights the relationship between maternal obesity and
the risk of preeclamsia,

Preeclampsia

Preeclampsia is a pregnancy-specific syndrome that complicates

approximately 3-6% of pregnancies, and is associated with a high
risk of preterm delivery, intrauterine growth restriction, placental
abruption, and perinatal mortality[17-20].The WHO reported that

ISSN: 2333-6439
Copyright
2014 Hiroaki et al.
OPEN ACCESS

Keywords
Pregnancy
Hypertension
Pregnancy-induced hypertension (PIH)
Developmental origins of health and diseases
(DOHaD)

that 784 of 2,538 cases of maternal near miss or maternal deaths

in 29 countries cases (25.9%) had eclampsia or preeclampsia [21]
and that haemorrhage and hypertensive disorders were major
contributors to maternal deaths in developing countries [22].
Reducing the number of maternal deaths is a high priority for
the international community, especially in view of the increased
attention on Millennium Development Goals [22]. Previous studies
have suggested that preeclampsia may serve as a sentinel marker
for women at risk of cardiovascular, cerebrovascular, and/or
other chronic diseases later in life [23-26].The central dogma of
the pathophysiology of preeclampsia is that a reduction in organ
perfusion develops secondary to vasospasm and activation of
the coagulation cascade; however, the exact cause as well as
pathophysiology of preeclampsia remains elusive despite extensive
research [27-29].

Obesity in pregnancy

Obesity in pregnancy was recognized to increase the risk

of gestational diabetes mellitus, hypertension, preeclampsia,
cesarean delivery, postpartum weight retention, preterm
delivery, still birth, congenital anomalies including neural
tube defects, spontaneous abortion, recurrent miscarriage,
macrosomia, birth injury, difficulties related to anesthesia
management, and emergency cesarean section, more than 50
years ago [7,30-48]. Therefore, a recent marked increase in the
incidence of overweight and obese women of childbearing age has
raised specific issues related to their management in pregnancy.

Obesity in pregnancy and preeclampsia

Maternal obesity is a well-known risk factor for the

Cite this article: Itoh H, Kanayama N (2014) Obesity and Risk of Preeclampsia. Med J Obstet Gynecol 2(2): 1024.

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development of preeclampsia [12,49-51]. Several large
population studies have shown that obese women are two to
three times more likely to develop preeclampsia than their leaner
counterparts [35,36,42,51]. A population-based study of 159,072
singleton births in U.S.A. reveled that not only obese women
(prepregnancy body mass index [BMI]30.0),but also overweight
women (prepregnancy BMI=25.029.9) were at a significantly
higher risk for preeclampsia (Odds ratio 2.0 and 3.3, respectively)
than women with a prepregnancy BMI of less than 20.0 [35]. A
British population-based study of 287,213 births reported that
the incidence of preeclampsia was significantly higher in obese
women (prepregnancy BMI30.0; Odd ratio 2.14)as well as
overweight women (prepregnancyBMI=25.029.9; Odd ratio
1.44) than in women with aprepregnancy BMI of 20.0-24.9 [36].A
population-based study of 972,806 births in Sweden revealed that
obese women (prepregnancy BMI 29.1-30.0, prepregnancy BMI
35.1-40.0, prepregnancy BMI >40) were at a significantly higher
risk of preeclampsia (Odds ratio 2.62, 3.90 and 4.82, respectively)
than women with a prepregnancy BMI of 19.8-26.0 [42]. Kumari
et al., reported that 57 cases of preeclampsia (28.7%) among 188
extremely obese women with BMI>40 [52]. Lisonkova et. al., also
reported a strong association between maternal obesity and the
risk of early-onset preeclampsia [53].

Risk of preeclampsia and prepregnancy metabolic

disorders due to obesity

An overlapping spectrum of disorders is commonly observed

in obese women [36,54,55] and obesity is hypothesized to play a
central role in the concept of metabolic syndrome[56]. Chronic
hypertension, insulin resistance and/or hypertriglyceridemia
may be present prior to conception in obese women. Insulin
resistance as well as hypertriglyceridemia are risk factors
for preeclampsia [57-59], and are also important cofactors
in the development of endothelial dysfunction [60-62].Since
endothelial dysfunction is hypothesized to play a central role
in the pathogenesis of preeclampsia[63], it is plausible that the
prepregnancy presence of endothelial dysfunction by insulin
resistance and/or hypertriglyceridemia may be causatively
associated with the high incidence of preeclampsia in obese
pregnant women [49]. Therefore, the association between
maternal obesity and preeclampsia is sometimes confused by the
presence of metabolic syndrome due to obesity. However, Jensen
et al., studied 2,459 women with normal glucose tolerance and
found that the incidence of preeclampsia was still significantly
higher in obese women (prepregnancy BMI30.0; Odd ratio 5.6)
and overweight women (prepregnancyBMI=25.029.9; Odd ratio
1.7) than in women with a prepregnancy BMI of 18.5-24.9 [64].
OBrien et al., carried out a systemic review of 13 studies, which
included nearly 1.4 million women, and reported that the risk of
preeclampsia rose with increasesin BMI, even after adjustments
for other clinical and metabolic confounding factors [50].

Prevalence of preeclampsia and obesity

Preeclampsia has increased in both the youngest and oldest

women of the reproductive generation [65,66].The incidence of
preeclampsia has increased from 2.5% in 1987 to 3.2% in 2004in
the United States [67].This increase may have been influenced by
a variety of factors, including age groups, period effect, changes
Med J Obstet Gynecol 2(2): 1024 (2014)

in diagnostic criteria, and the earlier identification of symptoms

during pregnancy. Women born in the older cohorts may have
different lifestyle factors, such as smoking or illicit drug use, than
women born in more recent cohorts. Among these numerous
factors, an increase in obesity among women of reproductive age
is expected to be one of the strongest risk factors underlying the
increasing prevalence of preeclampsia [65,68,69]. Population
level variations in obesity have been shown to differ according to
both age and time period [70] and higher rates of preeclampsia
in populations with higher proportions of obese women are
expected; therefore, a birth cohort effect explaining trends over
time may occur. Previous studies have reported the presence of
cohort effects in obesity rates over time, which suggests that such
effects may then extend to cohort effects in preeclampsia[71,72].
Ananth et al. investigated 120 million women and concluded that
changes in the population prevalence of obesity were associated
with the period and cohort trends in preeclampsia, but did not
fully explain these trends [65].

Transgenerational risk of preeclampsia and possible

association with maternal obesity

Boyd et al., demonstrated that preeclampsia in a womans

family, but not in a mans family, was associated with a 24%163% increase in the risk of developing preeclampsia [73];
however, controversy surrounds the involvement of a mans
family [74].Genetic studies have failed to identify associations
between common genetic variants and the risk of preeclampsia
[75-77]. The mechanism underlying the transgenerational and/
or familial risk of preeclampsia has not yet been fully clarified,
although some studies have suggested the possible involvement
of large numbers of rare mutations [78,79].

On the other hand, maternal obesity, a well-established risk

factor of preeclampsia [12,49-51], elevates the risk of largefor-gestational-age infants [37,41,42,46] who are predisposed
to obesity during childhood and adolescent period [36,80,81].
Maternal obesity in pregnancy was shown to be tightly connected
to the developmental origins of obesity in the offspring [82-84].
An increasing amount of evidence has pointed to a possible
association between environmental aggression in utero and the
emergence of chronic diseases, such as obesity, throughout life,
leading to a new link between causality and the possibilities of
the early establishment of metabolic adjustments that determine
morbidity throughout life. This represents a new branch of
scientific knowledge known as the developmental origins of health
and disease (DOHaD)[85,86]. Therefore, it is speculated that
maternal obesity may increase the risk of preeclampsia in female
offspring due to a predisposition for obesity being involved, at
least partly, in the development of a transgenerational risk of
preeclampsia among obese pregnant women. More intensive
investigations are needed.

Lifestyle interventions for obese pregnant women

The current prevalence of obesity in the childbearing

generation poses a challenge to the management of pregnancy
as it is associated with adverse maternal and perinatal outcomes.
Lifestyle interventions, such as exercise and dietary interventions,
for general obesity are effective in some individuals, but
unsuccessful in the entire protestation against the increasing

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prevalence of obesity in developing as well as developed countries
[87]. Evidence for lifestyle interventions resulting in improved
pregnancy outcomes in obese pregnant women is conflicting [88].
Oteng-Ntim performed a systemic review and meta-analysis and
concluded that antenatal lifestyle interventions for obese women
before pregnancy were only effective in reducing gestational
diabetes, but not other complications [88]. Thangaratinam et al,.
carried out systemic reviews and meta-analysis and reported
that weight management interventions or dietary interventions
in obese pregnant women resulted in a significant reduction
in the incidence of preeclampsia [89]. The American College
of Obstetricians and Gynecologists (ACOG) recommended
that nutrition and exercise counseling should continue not
only antepartum, but also postpartum until attempting
another pregnancy for obese pregnant women [31]. A recent
Cochrane database showed that no randomized control trials
demonstrated the effectiveness of reducing maternal weight in
obese pregnant women and also that there can be no practical
recommendation for obese pregnant women to intentionally
lose weight during the pregnancy period [90].To the best of our
knowledge, no studies have scientifically proven the effectiveness
of antepartum exercise to reduce the incidence of preeclampsia
in obese mothers, although Sui et al., proposed the possibility
that exercise during pregnancy may provide obese mothers with
positive psychological feelings and family influences, and advice
from health professionals [91].

CONCLUSIONS

Large population studies have shown that obese women are

two to three times more likely to develop preeclampsia than
their leaner counterparts. Therefore, the recent marked increase
in obesity in women of childbearing age has raised specific
concerns regarding the risk management of preeclampsia.
Since maternal obesity appears to shift their offspring toward a
predisposition to obesity, this cycle may continuously increase
not only the incidence of preeclampsia, but also numerous risk
factors associated with pregnancy during the next half century.
Lifestyle interventions before conception as well as postpartum
until attempting another pregnancy is the most effective
strategy to reduce the risks associated with pregnancy in obese
women; however, this has not been very successful. Since global
preventive medical care programs have been unsuccessful in
protecting against the overwhelming prevalence of the Obesity
Tsunami in developed as well as developing countries [92], new
medical care strategies, such as preemptive medicine (http://
www.nih.gov/strategicvision.htm), are needed.

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The authors thank Mrs Yumiko Yamamoto and Mrs Naoko

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Cite this article

Itoh H, Kanayama N (2014) Obesity and Risk of Preeclampsia. Med J Obstet Gynecol 2(2): 1024.

Med J Obstet Gynecol 2(2): 1024 (2014)

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