Original Research
Maternal Obesity and the Risk of Early-Onset
and Late-Onset Hypertensive Disorders
of Pregnancy
Matthew J. Bicocca, MD, Hector Mendez-Figueroa,
Downloaded from https://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3Le0ic6pTQVAkPIHH+KGau1fYAsMZPhRTKQ0n/B1TNmMoNjN2DHeqLg== on 07/11/2020
and Baha M. Sibai, MD
OBJECTIVE: To evaluate the relationship between
maternal body mass index (BMI) at delivery and rates
of early-onset and late-onset hypertensive disorders of
pregnancy.
METHODS: We performed a population-based, retro-
spective cohort study using U.S. Vital Statistics period-
linked birth and infant death certificates from 2014 to
2017. Women who delivered a nonanomalous singleton
live neonate from 24 to 41 completed weeks of gestation
were included. We excluded women with chronic hyper-
tension and those with BMIs less than 18.5. The primary
exposure was maternal BMI, defined as nonobese (BMI
18.5–29.9; referent group), class 1 obesity (BMI 30.0–
34.9), class 2 obesity (BMI 35.0–39.9), and class 3 obesity
(BMI 40.0 or greater). The primary outcome was delivery
with hypertensive disorders of pregnancy (gestational
hypertension, preeclampsia, or eclampsia) at less than
34 weeks of gestation or at 34 weeks or more. Multivari-
able Poisson regression was used to estimate relate risk
and adjust for confounding variables. Results are pre-
sented as adjusted relative risk (aRR) and 95% CIs.
RESULTS: Of the 15.8 million women with live births
during the study period, 14.0 million (88.6%) met
inclusion criteria, and 825,722 (5.9%) had hypertensive
disorders of pregnancy. The risk of early-onset hyper-
From the Department of Obstetrics, Gynecology and Reproductive Sciences,
McGovern Medical School, University of Texas Health Science Center at
Houston, Houston, Texas.
Each author has confirmed compliance with the journal’s requirements for
authorship.
Corresponding author: Matthew J. Bicocca, MD, Department of Obstetrics,
Gynecology and Reproductive Sciences, McGovern Medical School, University of
Texas Health Science Center at Houston, Houston, TX; email:
matthew.bicocca@uth.tmc.edu.
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2020 by the American College of Obstetricians and Gynecologists. Published
by Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0029-7844/20
118 VOL. 136, NO. 1, JULY 2020
© 2020 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
MD, Suneet P. Chauhan, MD, Hon DSc,
tensive disorders of pregnancy was significantly higher in
women with class 1 obesity (aRR 1.13; 95% CI 1.10–1.16),
class 2 obesity (aRR 1.57; 95% CI 1.53–1.62), and class 3
obesity (aRR 2.18; 95% CI 2.12–2.24), compared with
nonobese women. The risk of late-onset hypertensive
disorders of pregnancy was also significantly increased
in women with class 1 obesity (aRR 1.71; 95% CI 1.70–
1.73), class 2 obesity (aRR 2.60; 95% CI 2.58–2.62), and
class 3 obesity (aRR 3.93; 95% CI 3.91–3.96) compared
with nonobese women.
CONCLUSION: Compared with nonobese women, the
risk of early-onset and late-onset hypertensive disorders
of pregnancy is significantly and progressively increased
among women with increased class of obesity.
(Obstet Gynecol 2020;136:118–27)
DOI: 10.1097/AOG.0000000000003901
H
ypertensive disorders of pregnancy, which in-
cludes gestational hypertension, preeclampsia,
and eclampsia, affect 4–8% of pregnancies and are
a leading cause of maternal and neonatal morbid-
ity.1–3 In developed nations, preeclampsia is associ-
ated with a doubling in the rate of adverse neonatal
events, including sepsis, seizures and neonatal
death,4,5 and is responsible for 16% of maternal
deaths.6
One contemporary view of hypertensive disor-
ders of pregnancy differentiates two disease subtypes:
early-onset and late-onset.7–9 Early-onset disease (less
than 34 weeks of gestation) constitutes 5–10% of
hypertensive disorders of pregnancy and is associated
with a fivefold increased risk of perinatal death2 and
a twofold to fourfold increased risk of severe cardio-
vascular, renal, or hepatic maternal morbidity com-
pared with late-onset disease (34 weeks of gestation
or more).3 Early-onset and late-onset hypertensive
disorders of pregnancy share multiple risk factors,
including nulliparity, multiple gestation, advancing
OBSTETRICS & GYNECOLOGY
maternal age, African American race, chronic hyper-
tension, and diabetes mellitus.2,10–12 Although obesity
is an established risk factor for late-onset disease,6,13–16
there are conflicting reports about the link between
maternal body mass index (BMI, calculated as weight
in kilograms divided by height in meters squared) and
early-onset hypertensive disorders of pregnancy.17–24
The incongruencies in the literature regarding
obesity and early-onset hypertensive disorders of
pregnancy may be attributable to sample size, because
early-onset hypertensive disorders of pregnancy is
uncommon. We therefore undertook this analysis
using U.S. Vital Statistics data with the objective of
ascertaining whether the rate of early-onset and late-
onset hypertensive disorders of pregnancy is signifi-
cantly higher among obese women compared with
nonobese women.
METHODS
We performed a population-based, retrospective
cohort study using U.S. Vital Statistics period-linked
birth and infant death certificates from 2014 to 2017.
The data are compiled annually by the U.S. Center
for Health Statistics and undergo unified coding and
quality control before public release by the Centers
for Disease Control and Prevention. The methodol-
ogy for establishing the national linked record file is
discussed in the annual user guide, along with variable
definitions.25 The data are de-identified and deemed
exempt by the Institutional Review Board of the Uni-
versity of Texas Health Science Center at Houston
(IRB HSC-MS-16-0931). We included all singleton
pregnancies delivering from 24 to 41 completed
weeks of gestation. Exclusion criteria were chronic
hypertension, major fetal anomalies, missing hyper-
tension or diabetes status, missing maternal height
or weight, maternal height 48 inches or less, or mater-
nal BMI less than 18.5.
The demographic and outcome data collected by
birth and infant death certificates have undergone
multiple revisions. The 2003 revision replaced the
1989 revision, but uptake has been gradual and varied
across the United States. Fewer than 4% of births in
2014 used the 1989 revision, decreasing to 1.7% by
2015. In 2016 and 2017, the 2003 revision was used
exclusively. By limiting our analysis to births from
2014 to 2017 reported using the 2003 revision, we
sought to minimize the variations in reported demo-
graphics and outcomes,26 and also to standardize the
diagnosis of hypertensive disease after the release of
the Hypertension in Pregnancy Task Force Report by
the American College of Obstetricians and Gynecol-
ogists in November 2013.27
VOL. 136, NO. 1, JULY 2020 Bicocca et al
© 2020 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Our primary outcome was the diagnosis of
hypertensive disorders of pregnancy, which included
any of the following: gestational hypertension, pre-
eclampsia without severe features, preeclampsia with
severe features, and eclampsia. The 2003 birth certif-
icate revision does not include preeclampsia as
a separately reported condition, and all women with
gestational hypertension or preeclampsia were classi-
fied as gestational hypertension.26 Eclampsia was re-
corded as a separate variable. Chronic hypertension
was mutually exclusive with gestational hypertension,
making delineation of superimposed preeclampsia
unfeasible. To account for this limitation, all women
with chronic hypertension were excluded from our
analysis. Additionally, we considered all women with
eclampsia to have a hypertensive disorder of preg-
nancy, regardless of an independent diagnosis of ges-
tational hypertension.
Our primary exposure was maternal BMI at
delivery as a categorical variable. Body mass index
was divided into four mutually exclusive categories
based on the World Health Organization BMI classi-
fication: 18.5–29.9 (reference), 30.0–34.9 (class 1 obe-
sity), 35.0–39.9 (class 2 obesity), and 40.0 or greater
(class 3 obesity).28 Comparisons among groups were
made using Poisson regression with robust error var-
iance to estimate relative risk. Multivariate regression
was performed to control for maternal age (younger
than 18, 18–34, 35 years or older); race and ethnicity
(non-Hispanic white, non-Hispanic black, Hispanic,
Asian, other or unknown); education (less than high
school, high school or more, unknown); marital status
(married, single, unknown); prenatal care (yes, no,
unknown); smoking during pregnancy (yes, no,
unknown); nulliparity (yes, no); diabetes (gestational
or pregestational); maternal weight gain (above Insti-
tute of Medicine [IOM, now known as the National
Academy of Medicine] recommendations, not above
IOM recommendations); and birth year. Missing or
unknown values were included in the analysis as an
additional group of their respective covariate. Results
are presented as adjusted relative risks (aRR) with
95% CIs. The relationship between hypertensive dis-
orders of pregnancy and increasing BMI class was
assessed using Spearman’s correlation coefficient in
our crude and adjusted Poisson regression models.
The sample size for this analysis was determined
by the number of participants in the database. The
analysis was stratified by gestational age at delivery:
early-onset (less than 34 weeks of gestation) compared
with late-onset (34 weeks of gestation or more).
Gestational age reported in the birth registry was
established using the National Center for Health
Obesity and Early-Onset vs Late-Onset Preeclampsia 119
Fig. 1. Flowchart of patient eligibility. *Items not mutually exclusive. BMI, body mass index.
Bicocca. Obesity and Early-Onset vs Late-Onset Preeclampsia. Obstet Gynecol 2020.

Statistics obstetric estimate of gestation at delivery,
a technique previously described and shown to
correlate more accurately with early ultrasound esti-
mations than use of last menstrual period alone.29,30
Rates of hypertensive disorders of pregnancy were
calculated by analysis of all eligible pregnancies at
the beginning of the gestational age period of interest.
For early-onset hypertensive disorders of pregnancy,
we analyzed all eligible women who delivered from
24 to 41 completed weeks of gestation thus considered
at-risk for developing the disease. The primary out-
come was defined as delivery before 34 weeks of ges-
tation with a diagnosis of hypertensive disorders of
pregnancy. For late-onset hypertensive disorders of
pregnancy, only women delivering from 34 to 41
week were analyzed, and any diagnosis of hyperten-
sive disorders of pregnancy was considered a positive
finding. The analysis was then repeated with cohorts
subdivided into gestational age ranges of 24–27, 28–
30, 31–33, 34–36, and 37–41 weeks of gestation.
To examine the association of maternal BMI on
hypertensive disorders of pregnancy independent of
diabetes status, a sensitivity analysis was performed
which excluded all women with gestational or pre-
gestational diabetes. The results are similarly pre-
sented as aRR (95% CI). All statistics were performed
using Stata 16. The STROBE (Strengthening the
Reporting of Observational Studies in Epidemiology)
guidelines for reporting observational studies were
followed.31
RESULTS
Of the 15,818,980 births between 2014 and 2017,
14,018,228 (88.6%) were included in the analysis (Fig.
1). Among eligible births, 6,436,936 (45.9%) were
nonobese, 4,042,052 (28.8%) had class 1 obesity,
2,094,140 (14.9%) had class 2 obesity, and 1,445,100
(10.3%) had class 3 obesity. The overall rate of hyper-
tensive disorders of pregnancy was 5.9%, divided
between early-onset (0.3%) and late-onset (5.6%).
There were statistically significant differences
across BMI groups for all measured characteristics
(Table 1). Rates of both gestational and pregestational
diabetes increased progressively from 3.8% and 0.4%
in the nonobese group to 11.0% and 1.9% in the class
3 obesity group, respectively. Rates of gestational
weight gain above IOM recommendations were lower
in the nonobese group (40.2%), compared with all

120 Bicocca et al Obesity and Early-Onset vs Late-Onset Preeclampsia OBSTETRICS & GYNECOLOGY

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Unauthorized reproduction of this article is prohibited.
Table 1. Maternal Characteristics

BMI (kg/m2)
Total 18.5–29.9 30.0–34.9 35.0–39.9 40.0 or Higher
Characteristic (N514,018,228) (n56,436,936) (n54,042,052) (n52,094,140) (n51,445,100) P

Age (y) ,.001

Younger than 18 220,334 (1.6) 129,481 (2.0) 56,149 (1.4) 23,514 (1.1) 11,190 (0.8)
18–34 11,557,594 (82.5) 5,289,178 (82.2) 3,315,209 (82.0) 1,739,971 (83.1) 1,213,236 (84.0)
35 or older 2,240,300 (16.0) 1,018,277 (15.8) 670,694 (16.6) 330,655 (15.8) 220,674 (15.3)
Race and ethnicity ,.001
Non-Hispanic white 7,363,523 (52.5) 3,515,325 (54.6) 2,071,486 (51.3) 1,053,488 (50.3) 723,224 (50.1)
Non-Hispanic black 1,906,260 (13.6) 726,735 (11.3) 539,922 (13.4) 342,841 (16.4) 296,762 (20.5)
Hispanic 3,322,277 (23.7) 1,347,708 (20.9) 1,075,194 (26.6) 557,093 (26.6) 342,282 (23.7)
Asian 888,438 (6.3) 621,614 (9.7) 201,925 (5.0) 50,498 (2.4) 14,401 (1.0)
Other or unknown 537,730 (3.8) 225,554 (3.5) 153,525 (3.8) 90,220 (4.3) 68,431 (4.7)
Education ,.001
Less than high school 1,961,221 (14.0) 881,890 (13.7) 582,277 (14.4) 298,813 (14.3) 198,241 (13.7)
High school or more 11,906,958 (84.9) 5,479,259 (85.1) 3,417,124 (84.5) 1,775,535 (84.8) 1,235,040 (85.5)
Unknown 150,049 (1.1) 75,787 (1.2) 42,651 (1.1) 19,792 (1.0) 11,819 (0.8)
Marital status ,.001
Married 8,146,769 (58.1) 3,926,560 (61) 2,354,234 (58.2) 1,135,486 (54.2) 730,489 (50.6)
Not married 5,436,071 (38.8) 2,301,995 (35.8) 1,560,798 (38.6) 896,458 (42.8) 676,820 (46.8)
Unknown 435,388 (3.1) 208,381 (3.2) 127,020 (3.1) 62,196 (3.0) 37,791 (2.6)
Prenatal care ,.001
Yes 13,535,845 (96.6) 6,191,612 (96.2) 3,913,577 (96.8) 2,029,507 (96.9) 1,401,149 (97.0)
No 186,539 (1.3) 99,826 (1.6) 47,648 (1.2) 23,352 (1.1) 15,713 (1.1)
Unknown 295,844 (2.1) 145,498 (2.3) 80,827 (2.0) 41,281 (2.0) 28,238 (2.0)
Smoking during ,.001
pregnancy
Yes 1,042,618 (7.4) 470,041 (7.3) 277,069 (6.9) 165,514 (7.9) 129,994 (9.0)
No 12,877,840 (91.9) 5,920,087 (92.0) 3,737,682 (92.5) 1,914,727 (91.4) 1,305,344 (90.3)
Unknown 97,770 (0.7) 46,808 (0.7) 27,301 (0.7) 13,899 (0.7) 9,762 (0.7)
Nulliparous 4,481,021 (32.0) 2,219,619 (34.5) 1,237,827 (30.6) 607,736 (29.0) 415,839 (28.8) ,.001
Weight gain above IOM 8,106,409 (57.8) 2,586,426 (40.2) 2,996,656 (74.1) 1,537,319 (73.4) 986,008 (68.2) ,.001
recommendations
Gestational diabetes 796,898 (5.7) 245,632 (3.8) 226,781 (5.6) 165,341 (7.9) 159,144 (11.0) ,.001
Pregestational diabetes 99,611 (0.7) 22,579 (0.4) 26,541 (0.7) 22,812 (1.1) 27,679 (1.9) ,.001
Delivery year ,.001
2014 3,434,220 (24.5) 1,610,602 (25.0) 981,899 (24.3) 500,302 (23.9) 341,417 (23.6)
2015 3,518,902 (25.1) 1,628,367 (25.3) 1,010,781 (25.0) 521,663 (24.9) 358,091 (24.8)
2016 3,569,801 (25.5) 1,628,855 (25.3) 1,032,717 (25.6) 537,298 (25.7) 370,931 (25.7)
2017 3,495,305 (24.9) 1,569,112 (24.4) 1,016,655 (25.2) 534,877 (25.5) 374,661 (25.9)
BMI, body mass index; IOM, Institute of Medicine (now known as the National Academy of Medicine).
Data are n (%) unless otherwise specified.

classes of obesity (74.1%, 73.4%, and 68.2% for classes
1, 2 and 3, respectively).
The relative risk of early-onset hypertensive
disorders of pregnancy was significantly and pro-
gressively increased among women with class 1, class
2, and class 3 obesity compared with nonobese
women (Tables 2 and 3). After adjusting for potential
confounders, the increases remained significant. For
late-onset disease, the increased risk of hypertensive
disorders of pregnancy was more pronounced, as class
3 obese women had an approximately fourfold
increased risk of late-onset hypertensive disorders of
pregnancy compared with nonobese women. When
women with diabetes were excluded from the analy-
sis, the absolute rates of hypertensive disorders of
pregnancy decreased across all BMI classes; however,
the adjusted and unadjusted relative risks remained
similar (Table 2).
When gestational ages were subdivided, the rates
of hypertensive disorders of pregnancy increased
across all BMI groups with increasing gestational
age (Fig. 2 and Table 3). Higher levels of obesity were
associated with increased rates of hypertensive disor-
ders of pregnancy, a consistent trend across all

VOL. 136, NO. 1, JULY 2020 Bicocca et al Obesity and Early-Onset vs Late-Onset Preeclampsia 121

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Table 2. Rate of Delivery With Hypertensive Disorders of Pregnancy, Early-Onset Compared With Late-
Onset

BMI Total Live Rate/1,000 Live Unadjusted RR Adjusted RR Adjusted RR

Onset (kg/m2) Births n Births (95% CI) (95% CI) (95% CI)*

Early Total 14,018,228 48,007 3.42 (3.39–3.46)

18.5–29.9 6,436,936 15,430 2.40 (2.36–2.44) 1.00 1.00 1.00
(ref)
30.0–34.9 4,042,052 12,781 3.16 (3.11–3.22) 1.32 (1.29–1.35) 1.13 (1.10–1.16) 1.14 (1.11–1.17)
35.0–39.9 2,094,140 9,761 4.66 (4.57–4.75) 1.94 (1.90–1.99) 1.57 (1.53–1.62) 1.61 (1.56–1.66)
40.0 or 1,445,100 10,035 6.94 (6.81–7.08) 2.90 (2.83–2.97) 2.18 (2.12–2.24) 2.25 (2.19–2.32)
higher
Late Total 13,970,221 777,715 55.7 (55.6–55.8)
18.5–29.9 6,421,506 186,630 29.1 (28.9–29.2) 1.00 1.00 1.00
(ref)
30.0–34.9 4,029,271 221,105 54.9 (54.7–55.1) 1.88 (1.87–1.89) 1.71 (1.70–1.73) 1.72 (1.71–1.73)
35.0–39.9 2,084,379 177,774 85.3 (84.9–85.7) 2.92 (2.90–2.94) 2.60 (2.58–2.62) 2.64 (2.62–2.66)
40.0 or 1,435,065 192,206 133.9 (133.4–134.5) 4.59 (4.56–4.62) 3.93 (3.91–3.96) 4.04 (4.01–4.07)
higher
BMI, body mass index; RR, relative risk; ref, referent.
Adjusted for maternal age, race and ethnicity, education, marital status, prenatal care, smoking during pregnancy, nulliparity, diabetes,
maternal weight gain, and birth year.
Bold indicates significant difference.
* Excluding women with gestational or pregestational diabetes.

Table 3. Rate of Hypertensive Disorders of Pregnancy per 1,000 Live Births

Gestational Unadjusted RR Adjusted RR

Age (wk) BMI (kg/m2) Total Live Births n Rate/1,000 Live Births (95% CI) (95% CI)

24–27 Total 14,018,228 6,554 0.47 (0.46–0.48)

18.5–29.9 (ref) 6,436,936 2,337 0.36 (0.35–0.38) 1.00 1.00
30.0–34.9 4,042,052 1,678 0.42 (0.40–0.44) 1.14 (1.07–1.22) 1.03 (0.96–1.11)
35.0–39.9 2,094,140 1,278 0.61 (0.58–0.64) 1.68 (1.57–1.80) 1.43 (1.33–1.55)
40.0 or higher 1,445,100 1,261 0.87 (0.83–0.92) 2.40 (2.24–2.57) 1.91 (1.77–2.06)
28–30 Total 14,011,674 12,209 0.87 (0.86–0.89)
18.5–29.9 (ref) 6,434,599 4,090 0.64 (0.62–0.66) 1.00 1.00
30.0–34.9 4,040,374 3,237 0.80 (0.77–0.83) 1.26 (1.20–1.32) 1.08 (1.02–1.13)
35.0–39.9 2,092,862 2,435 1.16 (1.12–1.21) 1.83 (1.74–1.92) 1.48 (1.41–1.57)
40.0 or higher 1,443,839 2,447 1.69 (1.63–1.76) 2.66 (2.53–2.80) 2.03 (1.93–2.15)
31–33 Total 13,999,465 29,244 2.09 (2.07–2.11)
18.5–29.9 (ref) 6,430,509 9,003 1.40 (1.37–1.43) 1.00 1.00
30.0–34.9 4,037,137 7,866 1.95 (1.91–1.99) 1.39 (1.35–1.43) 1.18 (1.14–1.22)
35.0–39.9 2,090,427 6,048 2.89 (2.82–2.97) 2.06 (2.00–2.13) 1.65 (1.59–1.70)
40.0 or higher 1,441,392 6,327 4.39 (4.28–4.50) 3.13 (3.03–3.23) 2.31 (2.23–2.39)
34–36 Total 13,970,221 115,762 2.09 (2.07–2.11)
18.5–29.9 (ref) 6,421,506 30,501 4.75 (4.70–4.80) 1.00 1.00
30.0–34.9 4,029,271 31,183 7.74 (7.65–7.83) 1.62 (1.59–1.65) 1.38 (1.36–1.40)
35.0–39.9 2,084,379 25,223 12.1 (12.0–12.2) 2.54 (2.49–2.58) 2.03 (1.99–2.07)
40.0 or higher 1,435,065 28,855 20.1 (19.9–20.3) 4.22 (4.15–4.28) 3.12 (3.07–3.18)
37–41 Total 13,854,459 661,953 47.8 (47.7–47.9)
18.5–29.9 (ref) 6,391,005 156,129 24.4 (24.3–24.6) 1.00 1.00
30.0–34.9 3,998,088 189,922 47.5 (47.3–47.7) 1.91 (1.90–1.92) 1.76 (1.75–1.77)
35.0–39.9 2,059,156 152,551 74.1 (73.7–74.4) 2.98 (2.96–3.00) 2.69 (2.67–2.71)
40.0 or higher 1,406,210 163,351 116.2 (115.6–116.7) 4.69 (4.66–4.72) 4.10 (4.07–4.13)
BMI, body mass index; RR, relative risk; ref, referent.
Adjusted for maternal age, race and ethnicity, education, marital status, prenatal care, smoking during pregnancy, nulliparity, diabetes,
maternal weight gain, and birth year.
Bold indicates significant difference.

122 Bicocca et al Obesity and Early-Onset vs Late-Onset Preeclampsia OBSTETRICS & GYNECOLOGY

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Table 4. Rate of Hypertensive Disorders of Pregnancy per 1,000 Live Births, Excluding Women With
Gestational and Pregestational Diabetes

Gestational Rate/1,000 Unadjusted RR Adjusted RR

Age (wk) BMI (kg/m2) Total Live Births n Live Births (95% CI) (95% CI)

24–27 Total 13,121,719 5,973 0.46 (0.44–0.47)

18.5–29.9 (ref) 6,168,725 2,209 0.36 (0.34–0.37) 1.00 1.00
30.0–34.9 3,788,730 1,539 0.41 (0.39–0.43) 1.13 (1.06–1.21) 1.03 (0.96–1.11)
35.0–39.9 1,905,987 1,136 0.60 (0.56–0.63) 1.66 (1.55–1.79) 1.44 (1.34–1.56)
40.0 or higher 1,258,277 1,089 0.87 (0.81–0.92) 2.42 (2.25–2.60) 1.97 (1.82–2.13)
28–30 Total 13,115,746 10,830 0.83 (0.81–0.84)
18.5–29.9 (ref) 6,166,516 3,806 0.62 (0.60–0.64) 1.00 1.00
30.0–34.9 3,787,191 2,885 0.76 (0.73–0.79) 1.23 (1.17–1.29) 1.08 (1.02–1.13)
35.0–39.9 1,904,851 2,122 1.11 (1.07–1.16) 1.80 (1.71–1.90) 1.52 (1.44–1.61)
40.0 or higher 1,257,188 2,017 1.60 (1.54–1.68) 2.60 (2.46–2.74) 2.11 (1.99–2.24)
31–33 Total 13,104,916 24,382 1.86 (1.84–1.88)
18.5–29.9 (ref) 6,162,710 8,069 1.31 (1.28–1.34) 1.00 1.00
30.0–34.9 3,784,306 6,702 1.77 (1.73–1.81) 1.35 (1.31–1.39) 1.19 (1.15–1.23)
35.0–39.9 1,902,729 4,912 2.58 (2.51–2.65) 1.97 (1.90–2.04) 1.69 (1.63–1.76)
40.0 or higher 1,255,171 4,699 3.74 (3.64–3.85) 2.86 (2.76–2.96) 2.40 (2.31–2.49)
34–36 Total 13,080,534 92,661 7.08 (7.04–7.13)
18.5–29.9 (ref) 6,154,641 27,098 4.40 (4.35–4.46) 1.00 1.00
30.0–34.9 3,777,604 25,858 6.85 (6.76–6.93) 1.55 (1.52–1.57) 1.39 (1.36–1.41)
35.0–39.9 1,897,817 19,583 10.3 (10.2–10.5) 2.33 (2.29–2.37) 2.06 (2.02–2.11)
40.0 or higher 1,250,472 20,122 16.1 (15.9–16.3) 3.64 (3.57–3.71) 3.19 (3.13–3.25)
37–41 Total 12,987,873 577,488 44.5 (44.4–44.6)
18.5–29.9 (ref) 6,127,543 144,150 23.5 (23.4–23.7) 1.00 1.00
30.0–34.9 3,751,746 169,826 45.3 (45.1–45.5) 1.89 (1.88–1.90) 1.77 (1.75–1.78)
35.0–39.9 1,878,234 131,238 69.9 (69.5–70.2) 2.92 (2.90–2.94) 2.73 (2.71–2.75)
40.0 or higher 1,230,350 132,274 107.5 (107.0–108.1) 4.50 (4.46–4.53) 4.20 (4.17–4.23)
BMI, body mass index; RR, relative risk; ref, referent.
Adjusted for maternal age, race and ethnicity, education, marital status, prenatal care, smoking during pregnancy, nulliparity, diabetes,
maternal weight gain, and birth year.
Bold indicates significant difference.

gestational ages. After adjusting for potential con-
founding variables, the aRR of hypertensive disorders
of pregnancy was significantly increased for all BMI
groups at all gestational ages except class 1 obesity at
24–27 weeks of gestation (Fig. 3 and Table 3). The
same pattern persisted when patients with diabetes
were excluded from the analysis (Table 4).
DISCUSSION
Among a nationwide cohort of women, we noted that
increasing levels of maternal obesity are associated
with progressively increased risk of both early-onset
and late-onset hypertensive disorders of pregnancy.
This risk remained after adjustment for potential
confounders such as maternal age, race, or nullipar-
ity or when excluding patients with a synergistic
disease process such as diabetes. Moreover, the
increased risk of hypertensive disorders of preg-
nancy was evident as early as 24–27 weeks of gesta-
tion among women with class 2 and class 3 obesity.
Our observed rate of early-onset hypertensive disor-
ders of pregnancy (3.2/1,000) was consistent with
prior publications,17,18,21,24 as was the prevalence
of late-onset disease (55.7/1,000).17,21,24
The pathophysiology underlying early-onset
hypertensive disorders of pregnancy may be distinct
from late-onset hypertensive disorders of pregnancy,
which contributes to uncertainty regarding the role of
obesity. In early-onset disease, abnormal placentation
putatively results in chronic uteroplacental insuffi-
ciency, focal ischemia, and the eventual release of
inflammatory cytokines resulting in systemic maternal
hypertension.9,32,33 Conversely, late-onset hyperten-
sive disorders of pregnancy may be secondary to an
underlying placental insufficiency coupled with
chronic oxidative stress from maternal metabolic de-
rangements such as obesity and insulin resistance.7,9,32
Body mass index is therefore linked primarily with
late-onset hypertensive disorders of pregnancy, and
its role in early-onset disease is inconsistently
described.
Previous retrospective work by Ornaghi et al22
examined risk factors for early-onset and late-onset
hypertensive disorders of pregnancy and found BMI

VOL. 136, NO. 1, JULY 2020 Bicocca et al Obesity and Early-Onset vs Late-Onset Preeclampsia 123

© 2020 by the American College of Obstetricians

and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
 Fig. 2. Rate of hypertensive dis-
orders of pregnancy by body mass
index (BMI) and gestational age.
Bicocca. Obesity and Early-Onset vs
Late-Onset Preeclampsia. Obstet Gyne-
col 2020.

35.0 or greater to be an influencing factor only for
late-onset disease in a cohort of 284 women with
preeclampsia. Similar findings were reported by
Poon et al in a cohort of women with early-onset
preeclampsia, late-onset preeclampsia, and gesta-
tional hypertension, although they used a BMI cut-
off of 30.0.23 A smaller study by Fang et al
compared 150 women with preeclampsia (29 with
early-onset) with normotensive women in a control
group. In agreement with our data, they noted a sig-
nificant increase in risk of late-onset disease in
women with BMIs of 30.0 or greater, with a similar
trend for early-onset hypertensive disorders of preg-
nancy (adjusted odds ratio 4.07; 95% CI 0.81–20.42)
that was not statistically significant.20 A larger
cohort study by Durst et al of 10,196 women exam-
ined BMI as a risk factor for preeclampsia with
severe features. They reported an increased risk of
early-onset severe preeclampsia only in morbidly
obese women (BMI 40.0 or more) but increased
rates of late-onset disease in all overweight and
obese patients.19

Fig. 3. Results adjusted for maternal

age, race and ethnicity, education,
marital status, prenatal care, smok-
ing during pregnancy, nulliparity,
diabetes, gestational weight gain,
and birth year. Error bars represent
95% CIs. Body mass index (BMI) of
18.5–29.9 kg/m2 used as referent
group.
Bicocca. Obesity and Early-Onset vs
Late-Onset Preeclampsia. Obstet Gyne-
col 2020.

124 Bicocca et al Obesity and Early-Onset vs Late-Onset Preeclampsia OBSTETRICS & GYNECOLOGY

© 2020 by the American College of Obstetricians

and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
 Consistent with other large, population-based
studies, we note an association between both early-
onset and late-onset hypertensive disorders of preg-
nancy. Using Missouri birth certificate data
(n5854,085), Mbah et al21 showed the risk of early-
onset and late-onset preeclampsia progressively
increased with increasing levels of obesity. Their
adjusted odds ratios were similar to our reported
aRRs across all obesity classes, and differences in
reference groups (BMI 18.5–24.9 vs 18.5–29.9) and
their use of prepregnancy BMI likely accounts for
a portion of the observed discrepancy. Sohlberg
et al24 reported similar findings among Swedish
women with term preeclampsia (37 weeks of gesta-
tion or more), moderate early preeclampsia (32–36
weeks of gestation), and early preeclampsia (less than
32 weeks of gestation), but different gestational age
cutoffs makes direct comparison of risk assessment
difficult. Additional data by Catov et al18 suggest that
15–17% of the population risk of early-onset hyper-
tensive disorders of pregnancy is associated with
obesity, although their study defined early-onset as
less than 37 weeks of gestation.
The increasing prevalence of obesity in the
United States and worldwide highlights the impor-
tance of our findings and underscores the need for
prevention of hypertensive disorders of pregnancy in
this population.28,34 When initiated at less than 16
weeks of gestation, aspirin is effective in preventing
hypertensive disorders of pregnancy in high-risk pop-
ulations, but questions regarding appropriate dosing
in the obese population remain unanswered.35–37
Once at term, induction of labor at 39 weeks of ges-
tation prevents development of hypertensive disor-
ders of pregnancy in low-risk nulliparous women,38
and there have been progressively fewer late-term
and postterm pregnancies since the 1980s.39,40 These
interventions, along with changes in diagnostic crite-
ria, may contribute to the relatively slow increase in
rates of hypertensive disorders of pregnancy in the
face of the obesity epidemic.40
There are notable strengths to our study. The U.S.
Vital Statistics period-linked birth and infant death
certificates are compiled in a standardized fashion
across all 50 states and undergo quality control before
public release.25,26 The extensive demographic infor-
mation allows for analysis of potential confounding
variables and the large sample size is well suited to
study rare outcomes including early-onset hypertensive
disorders of pregnancy. Furthermore, the ability to sub-
divide the study population into narrow gestational age
groups allows delineation of trends, thus clarifying the
VOL. 136, NO. 1, JULY 2020 Bicocca et al
© 2020 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
effect of obesity in both early-onset and late-onset
hypertensive disorders of pregnancy.
We also acknowledge limitations in our study.
Maternal comorbidities within the U.S. Vital Statistics
database are limited to diabetes and hypertension, and
there is a possibility of unmeasured confounding
disease processes. Preeclampsia and gestational
hypertension could not be separately analyzed and
patients with chronic hypertension had to be excluded
as previously discussed. Additionally, we were limited
to gestational age at delivery and could not ascertain
gestational age at diagnosis of hypertensive disorders
of pregnancy. It is therefore probable that some
patients were diagnosed with early-onset hypertensive
disorders of pregnancy but delivered beyond 34
weeks of gestation and were, therefore, included in
our late-onset group. This would have occurred across
all BMI ranges and it is unlikely to influence our
aRRs. Similar to Durst et al,19 we limited our analysis
to maternal BMI at delivery. Although prepregnancy
BMI is available in the U.S. Vital Statistics Database,
it is derived from maternal recall during the delivery
admission and is therefore subject to recall bias.41
Finally, because the associations noted were modest
with a large sample size, the possibility of false alarm
exists.42
In conclusion, we noted that increasing classes of
obesity are associated with progressively increased
risk of both early-onset and late-onset hypertensive
disorders of pregnancy, with significant differences
apparent by 24 weeks of gestation. The larger effect of
obesity on rates of hypertensive disorders of preg-
nancy at later gestational ages is consistent with the
contemporary hypothesis that hypertensive disorders
of pregnancy is the result of multiple pathways
culminating in a single disease phenotype; addition-
ally, the dichotomous distinction between early-onset
and late-onset disease appears to overlap given the
early and progressive influence of obesity on rates of
hypertensive disorders of pregnancy.
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PEER REVIEW HISTORY
Received February 15, 2020. Received in revised form March 19,
2020. Accepted March 26, 2020. Peer reviews and author corre-
spondence are available at http://links.lww.com/AOG/B901.

VOL. 136, NO. 1, JULY 2020 Bicocca et al Obesity and Early-Onset vs Late-Onset Preeclampsia 127

© 2020 by the American College of Obstetricians

and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.