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OBSTETRICS
Early-pregnancy percent body fat in relation
to preeclampsia risk in obese women
Lindsay K. Sween, MD; Andrew D. Althouse, PhD; James M. Roberts, MD

OBJECTIVE: The purpose of this study was to identify differences of (measured at 10.2  3.0 weeks of gestation) as predictors of
early-pregnancy body fat percentage and body mass index (BMI) preeclampsia outcomes.
between obese women that experienced preeclampsia and those
RESULTS: Three hundred seventy-three women were included in the
who did not.
analysis: 30 women had preeclampsia by clinical definition (8.0%),
STUDY DESIGN: We performed an analysis of the Prenatal and 14 women had preeclampsia by the research definition (3.8%).
Exposures and Preeclampsia Prevention 3 longitudinal cohort There was no relationship between BMI and preeclampsia risk in
study of preeclampsia mechanisms in obese and overweight obese women; however, body fat percentage was associated signifi-
women. Women completed questionnaires regarding their health cantly with increased risk of both the clinical definition of preeclampsia
behaviors; had hematocrit level, weight and height, and waist and and the research definition. In 239 obese women, a 1% increase in
hip circumferences measured, and had resistance and reactance body fat was associated with approximately 12% increased odds of
measured by bioelectric impedance analysis machine during the clinical preeclampsia and 24% increased risk of preeclampsia by the
first, second, and third trimesters. Total body water, fat mass, and research definition.
percent body fat were calculated with the use of pregnancy-
CONCLUSION: Early-pregnancy body fat appears to be important in the
specific formulas. Preeclampsia was assessed with the clinical
pathophysiologic condition of preeclampsia in obese women.
definition and a research definition (clinical preeclampsia
plus hyperuricemia). Logistic regression models were constructed Key words: bioelectric impedance analysis, body fat percentage, body
to analyze early-pregnancy BMI and body fat percentage mass index, obesity, preeclampsia

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.

P reeclampsia is a serious pregnancy


complication that occurs in 5-8%
of pregnancies in the United States1 and
In this study, we hypothesized that the
amount of body fat may help to deter-
mine which obese women will experi-
recommended as an approach to the
assessment of this variable in pregnant
women.5,6 In this study, we used BIA to
accounts for approximately 15% of all ence preeclampsia. Prepregnancy BMI measure body fat in a large population
preterm births.2 Maternal prepregnancy has been used to dene obesity, but BMI of pregnant obese women and examined
obesity is one of the strongest potentially is not an optimal indicator of percent the relationship of rst-trimester
modiable risk factors for preeclamp- body fat in general and is even less reli- percent body fat to preeclampsia in
sia.3 There is a dose-response relation- able in pregnancy.5 Bioelectric imped- obese women.
ship between prepregnancy body mass ance analysis (BIA) is an alternative
index (BMI) and the risk of a woman evaluation of obesity. This approach
M ATERIALS AND M ETHODS
experiencing either mild or severe allows the estimation of body fat in large
Study population
preeclampsia.3,4 populations noninvasively and has been
Samples were collected as part of the
Prenatal Exposures and Preeclampsia
Prevention 3 Study, a longitudinal
From the Departments of Obstetrics, Gynecology, and Reproductive Sciences (Drs Althouse and
Roberts), Epidemiology (Dr Roberts), and Clinical and Translational Research (Dr Roberts), University cohort study of preeclampsia mecha-
of Pittsburgh School of Medicine (Dr Sween), and Magee-Womens Research Institute (Drs Althouse nisms in obese and overweight women
and Roberts), Pittsburgh, PA. that was approved by the University of
Received May 14, 2014; revised July 14, 2014; accepted July 30, 2014. Pittsburgh institutional review board; all
Supported by National Institutes of Health grant number P01 HD030367. women gave informed consent. Lean
The contents of this report represent the views of the authors and not necessarily those of the women were recruited in smaller
National Institutes of Health. numbers to compare any ndings in
The authors report no conict of interest. overweight and obese women with and
Corresponding author: James M. Roberts, MD. jroberts@mwri.magee.edu without preeclampsia to ndings in
0002-9378/$36.00  2015 Published by Elsevier Inc.  http://dx.doi.org/10.1016/j.ajog.2014.07.055 normal weight women. Women
with preexisting hypertension, diabetes

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mellitus, renal disease, other medical reactance measured by a BIA machine denition of preeclampsia in the re-
complications, or multiple gestations and the patients height, weight, sults.1 In previous studies, we found
were excluded. Women were recruited in abdominal circumference, and hemat- that a research denition (adds to the
early pregnancy from the outpatient ocrit level. TBW during pregnancy was American College of Obstetricians and
clinics of Magee-Womens Hospital in calculated with the equation deter- Gynecologists clinical denition an in-
Pittsburgh, PA, and had body composi- mined by Lukaski et al7 (Table 1). TBW crease of >30 systolic and/or >15 dia-
tion assessed by bioelectrical impedance was then used to estimate the weight of stolic above blood pressure at <20
in the rst, second, and third trimesters body fat. We derived an equation for weeks of gestation and hyperuricemia
(at approximately 10, 20, and 35 weeks weight of fat mass at any gestational age that is dened as 1 standard deviation
of gestation). The outpatient clinics based on the equations provided by van of uric acid concentration above the
serve primarily low-income, uninsured, Raaij et al.8 Water content of fat free mean for gestational age) denes a
unmarried, black, or biracial women; mass was calculated using two separate more severe and homogeneous pre-
373 women had complete early- equations, one for 0 to 10 weeks of eclampsia population.9-11 Thirty wo-
pregnancy (rst trimester) data and gestation and one for 10 to 40 weeks of men in the study cohort met the
were eligible for inclusion in this study. gestation, that were derived from American College of Obstetricians and
Figure 1 of van Raaij et al.8 These Gynecologists criteria for clinical pre-
Measurements equations were validated against eclampsia that was dened earlier; 14
Women completed a questionnaire deuterium dilution spaces7 and under- of these women also met the more
regarding their health behaviors, repro- water weighing.8 restrictive research denition.
ductive history, and demographic char- Hematocrit level was measured in Blood pressure was determined by the
acteristics. Standing height and waist blood samples that were obtained by average of 5 pressures taken after hos-
and hip circumferences were measured venipuncture. pital admission for delivery and before
twice for accuracy, and the mean of the 2 the administration of any medications
values was used. Waist circumference Preeclampsia definition that would alter blood pressure. Pro-
was measured at the natural waist with We used 2 denitions of preeclampsia. teinuria was dened as >0.3 g of protein
the center of the navel as a physical The rst matches the current American in a 24-hour urine collection, 2 protein
landmark. Hip circumference was College of Obstetrics and Gynecology measured by dipstick in a random urine
measured just below the bony promi- denition when we began the study, in sample, a catheterized urine sample with
nence of the anterior superior iliac spine. which a woman with previously normal 1 protein, or a protein-creatinine ratio
Early pregnancy BMI was calculated blood pressure has a blood pressure >0.3. A jury reviewed the abstracted
from weight and height measurements at 140 and/or 90 mm Hg after 20 medical records to determine that
the rst visit (at 10.3  2.9 weeks of weeks of gestation and proteinuria; criteria for preeclampsia had been
gestation). we will refer to this as the clinical satised.
Resistance and reactance were
measured with a Quantum IV Bioelec-
trical Impedance Analyzer (RJL Systems,
Clinton Township, MI). Measurements TABLE 1
were taken with the patient lying supine Body composition equations
with arms at a 30-degree angle from the Variable Equation
body and with the legs not touching so as Total body water, L 7
TBW 0.7*(height [cm]2/resistance)
not to disrupt the electrical circuit. 0.051*(abdominal circumference [cm]) 
Electrodes were attached in a tetrapolar 0.069*(weight [kg])  0.029*(reactance) 
arrangement, with 2 electrodes on the 0.043*(hematocrit) 2.833
dorsal surface of the right foot and 2 Weight of fat mass, kg8
electrodes on the dorsal surface of the 10 wk WFM WB  TBW/0.725
right hand, 1 proximally and 1 distally.
20 wk WFM WB  TBW/0.732
The distal electrodes act as the gener-
ating electrodes that transmit a small, 30 wk WFM WB  TBW/0.740
painless electrical current; the proximal 40 wk WFM WB  TBW/0.750
electrodes receive the electric current Water content of fat-free mass, % 8
and measure the voltage drop between
the right hand and right foot.5 0-10 wk y 0.724 0.0001*GA
0-40 wk y 0.00000666*GA2 0.0005*GA 0.719
Body composition calculations GA, gestational age; TBW, total body water; WB, bodyweight.
BIA theory estimates total body water Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.
(TBW) based on the resistance and

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Statistical methods values < .05 were considered statistically preeclampsia risk by both the research
Baseline data were described with the signicant. and clinical denition. For each 1% in-
mean  standard deviation for contin- crease in body fat, the risk of clinical
uous variables and percentages for cate- R ESULTS preeclampsia increased 12% (odds ratio
goric variables in the total population Study participants were aged 23.7  4.1 [OR], 1.124; 95% condence interval
and separately by preeclampsia status. years; 63% of them were black, and [CI], 1.018e1.240), and the risk of
Potential differences between women 20% of them were smokers (Table 2). preeclampsia by the research denition
with normal pregnancies or with pre- The average BMI was 33.1  7.8 kg/m2; increased 24% (OR, 1.239; 95% CI,
eclampsia were evaluated with the use of by study design, most participants were 1.054e1.455). These relationships were
t tests for continuous variables (equal overweight (22.0%) or obese (64.1%). strengthened slightly when we adjusted
variances unless otherwise called for; Gestational diabetes mellitus was the model for age, race, and smoking
unequal variances test used where more common in women in the both status (Table 4). We considered models
appropriate) and c2 tests for categoric clinical (6.9%) and research-denitions that included both BMI and percent
differences (Fisher exact test in cases of preeclampsia (14.3%) than in those body fat together; in most of these
where expected cell counts were <5). with no preeclampsia (3.5%). Mean models, percent body fat showed a
This study focused on early pregnancy gestational age at delivery was 39.5  stronger relationship than did BMI.
BMI and body fat percentage as pre- 1.3 weeks (39.0  1.3 weeks for the 30 However, with the small number
dictors of preeclampsia outcomes; women with clinical preeclampsia and of cases, including 2 highly correlated
therefore, rst-trimester measurements 38.1  1.7 weeks for the 14 women variables in a single model, resulted in
of BMI and body fat were used in all with research preeclampsia). There model instability that was caused by
primary analyses. Body fat percentage were no signicant differences in the variance ination. Similarly, we asked
was examined as a function of BMI; the distribution of obesity metrics (BMI, whether the relationships between body
Pearson correlation coefcient is pre- waist circumference, waist-hip ratio, fat/BMI and preeclampsia might be
sented to assess the linear relationship. or body fat percentage) in the 30 dependent on central obesity as indi-
Lacking sufcient sample size to test women with clinical or the 14 women cated by waist circumference or waist/
appropriately for interaction between with research preeclampsia compared hip ratio, but there was no interaction
BMI and percent body fat, we instead with the 343 normal pregnancies with either of these variables in the
assessed the relationship between body (Table 2). model (P > .05 for all).
fat and preeclampsia by testing for dif- There was a moderate linear correla- In models that were stratied by race,
ferences in percent body fat between tion between early-pregnancy body fat the ORs were generally similar for white
women with preeclampsia and healthy percentage and BMI (R2 0.66; Figure), and black women. For clinical pre-
control subjects within each of the World but it was not a perfect linear correlation, eclampsia, the OR was 1.15 (95% CI,
Health Organization BMI classications which suggests that body fat percentage 0.98e1.36) for white women, compared
using t tests (a test with unequal variance may offer independent information with of the OR of 1.02 (95% CI,
where appropriate). Logistic regression about preeclampsia risk. 0.95e1.11) for black women. By the
models were constructed to analyze BMI When we analyzed the mean body fat research denition, the OR for white
and body fat percentage as continuous percentage in women within World women was 1.15 (95% CI, 0.95e1.39)
variables and allow adjustment for a Health Organization BMI classications, compared with 1.29 (95% CI,
limited selection of potential con- only in the highest category of obese 1.04e1.61) for black women. We did not
founders. Because the Prenatal Expo- women (BMI >40 kg/m2) was the body have a sufciently large sample to
sures and Preeclampsia Prevention 3 fat percentage signicantly higher in formally test interaction by race.
study was designed to compare obese women who experienced preeclampsia When we examined these relation-
women who did or did not experience compared with those women who did ships in all women (including the lean
preeclampsia, we initially limited our not (Table 3). and overweight women), neither BMI
logistic regression models only to obese We compared BMI and percent nor body fat percentage was associated
women. We also performed a secondary body fat as predictors of preeclampsia signicantly with increased risk of pre-
analysis that included all participants in obese women (BMI 30 kg/m2; eclampsia by the clinical denition or
because of the surprisingly high rates Table 4). Higher BMI was associated the research denition (Table 5), which
of preeclampsia in the lean and over- signicantly with higher risk for the suggested that the relationship between
weight women (by the clinical deni- research denition of preeclampsia, but percent body fat and preeclampsia
tion, 7.69% of lean women and 6.31% of not the clinical denition. The effect was was present only in the obese women.
overweight women experienced pre- no longer signicant after adjustment These relationships did not vary signi-
eclampsia). All statistical analyses were for age, race, and smoking status. In cantly when we adjusted for gestational
performed with SAS software (version contrast, there was a signicant rela- diabetes mellitus, waist circumference,
9.4; SAS Institute, Cary, NC); probability tionship between percent body fat and or waist/hip ratio.

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TABLE 2
Baseline characteristics of study participants
All No preeclampsia Clinical preeclampsia Research preeclampsia
Characteristic (n [ 373) (n [ 343) (n [ 30) P valuea (n [ 14) P valueb
Age, y 23.7  4.1 23.7  4.1 23.3  4.8 .62 24.9  6.3 .30
Race, %
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 0 0
Smoking, % 20.1 21.3 6.7 .05 0 .08
Gestational age at enrollment, wk 10.2  3.0 10.3  2.9 9.6  3.1 .22 9.0  2.8 .10
Gestational age at delivery, wk 39.5  1.4 39.5  1.3 39.0  1.6 .05 38.1  1.7 .01
Gestational diabetes mellitus, % 3.8 3.5 6.9 .35 14.3 .02
Body mass index
At enrollment, kg/m2 33.1  7.8 33.0  7.7 33.4  8.5 .79 34.8  11.2 .40
JANUARY 2015 American Journal of Obstetrics & Gynecology

Classification, %
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

Obstetrics
Waist circumference, mm 1003  168 1002  168 1011  175 .78 1028  206 .57
Waist-hip ratio 0.86  0.07 0.86  0.07 0.87  0.08 .68 0.88  0.07 .30
Body fat percentage 45.9  10.2 45.8  10.1 46.9  11.3 .57 48.6  12.5 .31
a
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.

Research
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.
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might directly impair implantation.4,12


FIGURE Potential covariants with obesity include
The relationship between BMI and percentage of body fat diet, exercise, and fat distribution. We
No preeclampsia
did not account for the diet or exercise
habits of the women in our study. Fat
Preeclampsia distribution, as approximated by waist
80 circumference and waist-hip ratio,
was not associated signicantly with
70 R = 0.663
increased preeclampsia risk nor did it
60
increase the impact of higher body fat
percentage.
50 This study used BIA as a more direct
% Body Fat

way than BMI to measure fat mass dur-


40 ing pregnancy. The BIA analyzer com-
putes resistance and reactance, which
30
can be used to calculate TBW with the
20
use of algorithms largely developed
for nonpregnant women. Volume cal-
10 culations can be affected signicantly by
the expansion of the extracellular uid
0 compartment and the changes in he-
0 10 20 30 40 50 60 70
BMI (kg/m2)
matocrit level during pregnancy.5 To
nd a standard by which to compare BIA
The plus sign indicates no preeclampsia; the open circle indicates preeclampsia (clinical definition).
measurements in pregnancy, pregnancy-
BMI, body mass index.
specic formulas can be used to calculate
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.
TBW and then to convert it to body fat
mass.8 We did not validate BIA with
deuterium dilution spaces; however,
C OMMENT to include fetal/placental and maternal previous studies have shown that BIA
Our results demonstrate that, among contributions.13 The maternal contri- gives TBW estimates similar to dilution
obese participants, increasing body fat bution is posited to include predisposing values.6,7 Van Loan et al6 found that
percentage predicts increased risk of environmental, genetic, and behavior- TBW by dilution spaces in 10 healthy
preeclampsia by both the clinical and al responses to factors produced by pregnant women was 33.1  5.1 L at 8-
research denitions. Although the exact the insufciently perfused placenta.2 10 weeks of gestation, 36.1  4.1 L at 24-
mechanisms underlying this connection Obesity is one such risk factor that is 26 weeks, and 38.7  3.9 L at 34-36
remain unidentied, the nding that associated with inammation and weeks.6 Our results for TBW in the
body fat content more accurately pre- oxidative stress that are proposed to be healthy women without preeclampsia
dicts preeclampsia than does BMI sug- components in the pathophysiologic were in agreement with these deuterium
gests adipose tissue itself may be involved condition of preeclampsia.2,4 A high dilution spaces values: 34.4  7.4 L at
in the pathophysiologic condition of degree of maternal adiposity and asso- 10.3  2.9 weeks of gestation, 35.8 
preeclampsia. Preeclampsia is proposed ciated metabolic abnormalities also 5.8 L at 20.0  1.6 weeks, and 39.5  7.0 L

TABLE 3
Distribution of body fat percentages
No preeclampsia Preeclampsia
Body mass index classification n Mean body fat, % SD n Mean body fat, % SD P value
Lean 48 31.5  8.1 4 34.1  10.1 .54
Overweight 75 42.1  7.6 7 38.2  7.3 .20
Obese class 1 104 47.2  6.5 7 46.3  7.2 .73
Obese class 2 53 49.2  7.9 6 52.0  5.4 .40
Obese class 3 63 56.0  5.7 6 61.2  2.6 .03
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.

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TABLE 4
Relationships between body fat percentage and risk of preeclampsia: obese participants only
Odds ratio
Predictor Outcome Unadjusted 95% confidence interval Adjusteda 95% confidence interval
Body mass index Clinical preeclampsia (n 19) 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 Clinical preeclampsia (n 19) 1.124 1.018e1.240 1.127 1.009e1.257
Research preeclampsia (n 8) 1.239 1.054e1.455 1.294 1.060e1.581
a
Adjusted for age, race, and smoking status.
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.

at 35.2  0.9 weeks. Body fat percentage values were not signicant. Because of preeclampsia than do obese white
as calculated by pregnancy-specic BIA study design, our sample had low women.3,15 Furthermore, this study was
models also seems to agree with ndings numbers of lean and overweight women designed to recruit women with BMI
in studies that used hydrostatic weigh- (total 35.9%), which may not result in a >30 kg/m2, and most studies that have
ing. Previous studies that used this dispersal of data sufcient to demon- investigated the relationship between
technique have found body fat percent- strate a relationship. Alternatively, there prepregnancy BMI and preeclampsia
age to be 29.6  6.15% in healthy, lean may truly not be a relationship between have had small sample sizes of women
women at 30 weeks of gestation.8,14 The body fat percentage and preeclampsia with BMI >35 kg/m2. Bodnar et al4
average body fat percentage among the risk in women with a low amount of body found that the ORs of preeclampsia
lean women in our study at 35 weeks of fat. There was also a surprisingly high began trending downward after BMI 35
gestation (n 13) was similar (29.6  incidence of preeclampsia in lean and kg/m2, although they remained >1.0
7.3%). With all women in our study overweight women and a relatively low compared with BMI 21 kg/m2. Rela-
cohort included, the average body fat incidence in obese women in this study tionship between BMI and preeclampsia
percentage at 35 weeks of gestation was cohort (7.69% of lean women and 6.31% may become more ill-dened at very
45.3  8.9%, because of the large num- of overweight women, compared with high BMIs, given the varying percent
ber of overweight and obese women. 7.95% of obese women by the clinical body fat and body fat distributions (eg,
The relationship between body fat denition), which may blunt the re- central, abdominal, peripheral, or
percentage and preeclampsia risk was not lationships between BMI, body fat per- visceral) between obese individuals.
signicant when lean and overweight centage, and preeclampsia risk. Another Despite these possible explanations, both
women were included in the analysis, nor reason the expected relationship between the deviation from the well-established
was the usual relationship between prepregnancy BMI and the incidence of association between increasing BMI and
increasing BMI and increasing pre- preeclampsia was not seen could be elevated preeclampsia risk and the un-
eclampsia risk seen in this cohort. Both the predominance of obese black women usually high incidence of preeclampsia
increasing body fat percentage and BMI in the cohort. Several studies have among the lean and overweight women
trended towards increased preeclampsia determined that obese black women do raise questions about the representa-
risk with all women included, but the have a lower risk of the development of tive nature of this cohort.

TABLE 5
Relationships between obesity metrics and risk of preeclampsia: all patients
Odds ratio
Predictor Outcome Unadjusted 95% confidence interval Adjusteda 95% confidence interval
Body mass index Clinical preeclampsia (n 30) 1.006 0.960e1.055 1.008 0.961e1.057
Research preeclampsia (n 14) 1.028 0.964e1.096 1.025 0.963e1.091
Body fat Clinical preeclampsia (n 30) 1.011 0.973e1.050 1.009 0.971e1.048
Research preeclampsia (n 14) 1.030 0.973e1.092 1.034 0.977e1.094
a
Adjusted for age, race, and smoking status.
Sween. Percent body fat and preeclampsia risk. Am J Obstet Gynecol 2015.

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Another challenge encountered in this body fat percentage values. Further, we 6. Van Loan MD, Kopp LE, King JC, Wong WW,
study was the unusually high rates of did not adjust for multiple comparisons Mayclin PL. Fluid changes during pregnancy:
use of bioimpedance spectroscopy. J Appl
preeclampsia in the lean and overweight in our regression modeling, which Physiol 1995;78:1037-42.
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has not changed dramatically in our result being interpreted as positive; Total body water in pregnancy: assessment by
Pittsburgh population, which suggests however, we believed that the application using bioelectrical impedance. Am J Clin Nutr
that the high incidence of preeclampsia of a particularly harsh adjustment of the 1994;59:578-85.
8. van Raaij JMA, Peek MEM, Vermaat-
may be an aberrant nding that is related signicance level would have made it
Miedema SH, Schonk CM, Hautvast JGAJ. New
to the intentionally small numbers of impossible to detect any effect in a equations for estimating body fat mass in preg-
lean and overweight women. Alterna- cohort with relatively few cases. We nancy from body density or total body water. Am
tively, the cohort is 63% black women, adjusted the logistic regression model for J Clin Nutr 1988;48:24-9.
for whom the literature is mixed with age, race, and smoking during pregnancy 9. NHBPEPW Group. Report of the National
regards to preeclampsia risk.3,16,17 In one but could not account for other potential High Blood Pressure Education Program
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study, lean black women were more covariates, such as prepregnancy and Pregnancy. Am J Obstet Gynecol
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pertensive pregnancy: a retrospective cohort
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