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OBSTETRICS
Cite this article as: Sween LK, Althouse AD, Roberts JM. Early-pregnancy percent body fat in relation to preeclampsia risk in obese women. Am J Obstet Gynecol
2015;212:84.e1-7.
From the Departments of Obstetrics, Gynecology, and Reproductive Sciences (Drs Althouse and
Roberts), Epidemiology (Dr Roberts), and Clinical and Translational Research (Dr Roberts), University
of Pittsburgh School of Medicine (Dr Sween), and Magee-Womens Research Institute (Drs Althouse
and Roberts), Pittsburgh, PA.
Received May 14, 2014; revised July 14, 2014; accepted July 30, 2014.
Supported by National Institutes of Health grant number P01 HD030367.
The contents of this report represent the views of the authors and not necessarily those of the
National Institutes of Health.
The authors report no conict of interest.
Corresponding author: James M. Roberts, MD. jroberts@mwri.magee.edu
0002-9378/$36.00 2015 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ajog.2014.07.055
M ATERIALS
AND
M ETHODS
Study population
Samples were collected as part of the
Prenatal Exposures and Preeclampsia
Prevention 3 Study, a longitudinal
cohort study of preeclampsia mechanisms in obese and overweight women
that was approved by the University of
Pittsburgh institutional review board; all
women gave informed consent. Lean
women were recruited in smaller
numbers to compare any ndings in
overweight and obese women with and
without preeclampsia to ndings in
normal weight women. Women
with preexisting hypertension, diabetes
Obstetrics
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mellitus, renal disease, other medical
complications, or multiple gestations
were excluded. Women were recruited in
early pregnancy from the outpatient
clinics of Magee-Womens Hospital in
Pittsburgh, PA, and had body composition assessed by bioelectrical impedance
in the rst, second, and third trimesters
(at approximately 10, 20, and 35 weeks
of gestation). The outpatient clinics
serve primarily low-income, uninsured,
unmarried, black, or biracial women;
373 women had complete earlypregnancy (rst trimester) data and
were eligible for inclusion in this study.
Measurements
Women completed a questionnaire
regarding their health behaviors, reproductive history, and demographic characteristics. Standing height and waist
and hip circumferences were measured
twice for accuracy, and the mean of the 2
values was used. Waist circumference
was measured at the natural waist with
the center of the navel as a physical
landmark. Hip circumference was
measured just below the bony prominence of the anterior superior iliac spine.
Early pregnancy BMI was calculated
from weight and height measurements at
the rst visit (at 10.3 2.9 weeks of
gestation).
Resistance and reactance were
measured with a Quantum IV Bioelectrical Impedance Analyzer (RJL Systems,
Clinton Township, MI). Measurements
were taken with the patient lying supine
with arms at a 30-degree angle from the
body and with the legs not touching so as
not to disrupt the electrical circuit.
Electrodes were attached in a tetrapolar
arrangement, with 2 electrodes on the
dorsal surface of the right foot and 2
electrodes on the dorsal surface of the
right hand, 1 proximally and 1 distally.
The distal electrodes act as the generating electrodes that transmit a small,
painless electrical current; the proximal
electrodes receive the electric current
and measure the voltage drop between
the right hand and right foot.5
Body composition calculations
BIA theory estimates total body water
(TBW) based on the resistance and
Preeclampsia definition
We used 2 denitions of preeclampsia.
The rst matches the current American
College of Obstetrics and Gynecology
denition when we began the study, in
which a woman with previously normal
blood pressure has a blood pressure
140 and/or 90 mm Hg after 20
weeks of gestation and proteinuria;
we will refer to this as the clinical
Research
TABLE 1
Equation
TBW 0.7*(height [cm]2/resistance)
0.051*(abdominal circumference [cm])
0.069*(weight [kg]) 0.029*(reactance)
0.043*(hematocrit) 2.833
WFM WB TBW/0.725
20 wk
WFM WB TBW/0.732
30 wk
WFM WB TBW/0.740
WFM WB TBW/0.750
40 wk
8
y 0.724 0.0001*GA
0-40 wk
84.e2
Research
Obstetrics
Statistical methods
Baseline data were described with the
mean standard deviation for continuous variables and percentages for categoric variables in the total population
and separately by preeclampsia status.
Potential differences between women
with normal pregnancies or with preeclampsia were evaluated with the use of
t tests for continuous variables (equal
variances unless otherwise called for;
unequal variances test used where
appropriate) and c2 tests for categoric
differences (Fisher exact test in cases
where expected cell counts were <5).
This study focused on early pregnancy
BMI and body fat percentage as predictors of preeclampsia outcomes;
therefore, rst-trimester measurements
of BMI and body fat were used in all
primary analyses. Body fat percentage
was examined as a function of BMI; the
Pearson correlation coefcient is presented to assess the linear relationship.
Lacking sufcient sample size to test
appropriately for interaction between
BMI and percent body fat, we instead
assessed the relationship between body
fat and preeclampsia by testing for differences in percent body fat between
women with preeclampsia and healthy
control subjects within each of the World
Health Organization BMI classications
using t tests (a test with unequal variance
where appropriate). Logistic regression
models were constructed to analyze BMI
and body fat percentage as continuous
variables and allow adjustment for a
limited selection of potential confounders. Because the Prenatal Exposures and Preeclampsia Prevention 3
study was designed to compare obese
women who did or did not experience
preeclampsia, we initially limited our
logistic regression models only to obese
women. We also performed a secondary
analysis that included all participants
because of the surprisingly high rates
of preeclampsia in the lean and overweight women (by the clinical denition, 7.69% of lean women and 6.31% of
overweight women experienced preeclampsia). All statistical analyses were
performed with SAS software (version
9.4; SAS Institute, Cary, NC); probability
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values < .05 were considered statistically
signicant.
R ESULTS
Study participants were aged 23.7 4.1
years; 63% of them were black, and
20% of them were smokers (Table 2).
The average BMI was 33.1 7.8 kg/m2;
by study design, most participants were
overweight (22.0%) or obese (64.1%).
Gestational diabetes mellitus was
more common in women in the both
clinical (6.9%) and research-denitions
of preeclampsia (14.3%) than in those
with no preeclampsia (3.5%). Mean
gestational age at delivery was 39.5
1.3 weeks (39.0 1.3 weeks for the 30
women with clinical preeclampsia and
38.1 1.7 weeks for the 14 women
with research preeclampsia). There
were no signicant differences in the
distribution of obesity metrics (BMI,
waist circumference, waist-hip ratio,
or body fat percentage) in the 30
women with clinical or the 14 women
with research preeclampsia compared
with the 343 normal pregnancies
(Table 2).
There was a moderate linear correlation between early-pregnancy body fat
percentage and BMI (R2 0.66; Figure),
but it was not a perfect linear correlation,
which suggests that body fat percentage
may offer independent information
about preeclampsia risk.
When we analyzed the mean body fat
percentage in women within World
Health Organization BMI classications,
only in the highest category of obese
women (BMI >40 kg/m2) was the body
fat percentage signicantly higher in
women who experienced preeclampsia
compared with those women who did
not (Table 3).
We compared BMI and percent
body fat as predictors of preeclampsia
in obese women (BMI 30 kg/m2;
Table 4). Higher BMI was associated
signicantly with higher risk for the
research denition of preeclampsia, but
not the clinical denition. The effect was
no longer signicant after adjustment
for age, race, and smoking status. In
contrast, there was a signicant relationship between percent body fat and
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TABLE 2
All
(n [ 373)
No preeclampsia
(n [ 343)
Clinical preeclampsia
(n [ 30)
P valuea
Research preeclampsia
(n [ 14)
P valueb
23.7 4.1
23.7 4.1
23.3 4.8
.62
24.9 6.3
.30
White
35.2
35.1
36.7
.76
50.0
.65
Black
63.2
63.2
63.3
50.0
Other
1.6
1.8
Smoking, %
20.1
21.3
6.7
.05
.08
10.2 3.0
10.3 2.9
9.6 3.1
.22
9.0 2.8
.10
39.5 1.4
39.5 1.3
39.0 1.6
.05
38.1 1.7
.01
.35
14.3
.02
Age, y
Race, %
3.8
3.5
6.9
33.0 7.7
33.4 8.5
.79
34.8 11.2
.40
Lean
13.9
14.0
13.3
.89
14.3
.35
Overweight
22.0
21.9
23.3
28.6
Obese 1
29.8
30.3
23.3
14.3
Obese 2
15.8
15.5
20.0
7.1
Obese 3
18.5
18.4
20.0
35.7
At enrollment, kg/m2
Waist circumference, mm
Waist-hip ratio
Body fat percentage
a
1003 168
0.86 0.07
45.9 10.2
1002 168
0.86 0.07
45.8 10.1
1011 175
0.87 0.08
46.9 11.3
.78
.68
.57
1028 206
0.88 0.07
48.6 12.5
Derived from comparison of 30 participants with clinical preeclampsia vs 343 participants with no preeclampsia; b Derived from comparison of 14 participants with research preeclampsia vs 343 participants with no preeclampsia.
.30
.31
84.e4
Research
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.
.57
Obstetrics
Classification, %
Research
Obstetrics
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FIGURE
Preeclampsia
80
R = 0.663
70
% Body Fat
60
50
40
30
20
10
0
10
20
30
40
50
60
70
BMI (kg/m2)
The plus sign indicates no preeclampsia; the open circle indicates preeclampsia (clinical definition).
BMI, body mass index.
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.
C OMMENT
Our results demonstrate that, among
obese participants, increasing body fat
percentage predicts increased risk of
preeclampsia by both the clinical and
research denitions. Although the exact
mechanisms underlying this connection
remain unidentied, the nding that
body fat content more accurately predicts preeclampsia than does BMI suggests adipose tissue itself may be involved
in the pathophysiologic condition of
preeclampsia. Preeclampsia is proposed
TABLE 3
No preeclampsia
Preeclampsia
P value
48
31.5 8.1
34.1 10.1
.54
75
42.1 7.6
38.2 7.3
.20
Obese class 1
104
47.2 6.5
46.3 7.2
.73
Obese class 2
53
49.2 7.9
52.0 5.4
.40
Obese class 3
63
56.0 5.7
61.2 2.6
.03
Overweight
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.
Obstetrics
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Research
TABLE 4
Relationships between body fat percentage and risk of preeclampsia: obese participants only
Odds ratio
Predictor
Outcome
Unadjusted
Adjusteda
1.017
0.947e1.092
1.011
0.939e1.088
Research preeclampsia (n 8)
1.099
1.008e1.198
1.082
0.989e1.184
Body fat
1.124
1.018e1.240
1.127
1.009e1.257
Research preeclampsia (n 8)
1.239
1.054e1.455
1.294
1.060e1.581
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.
TABLE 5
Outcome
Body fat
a
Adjusteda
1.006
0.960e1.055
1.008
0.961e1.057
1.028
0.964e1.096
1.025
0.963e1.091
1.011
0.973e1.050
1.009
0.971e1.048
1.030
0.973e1.092
1.034
0.977e1.094
Unadjusted
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.
84.e6
Research
Obstetrics
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body fat percentage values. Further, we
did not adjust for multiple comparisons
in our regression modeling, which
allowed the possibility of a spurious
result being interpreted as positive;
however, we believed that the application
of a particularly harsh adjustment of the
signicance level would have made it
impossible to detect any effect in a
cohort with relatively few cases. We
adjusted the logistic regression model for
age, race, and smoking during pregnancy
but could not account for other potential
covariates, such as prepregnancy and
pregnancy diet and exercise habits.
This study supports the relationship
of fat to preeclampsia. Subsequent longitudinal, multicenter trials with larger
case numbers are needed to further
assess the utility of BIA-determined body
fat percentage in the prediction of preeclampsia onset.
-
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