Original Investigation | Obstetrics and Gynecology

Preeclampsia Prevalence, Risk Factors, and Pregnancy Outcomes

in Sweden and China
Yingying Yang, MD; Isabelle Le Ray, MD, PhD; Jing Zhu, MD, PhD; Jun Zhang, MD, PhD; Jing Hua, MD, PhD; Marie Reilly, PhD

Abstract Key Points

Question Does preeclampsia differ in
IMPORTANCE Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality
prevalence, risk factors, or pregnancy
worldwide. Within-country studies have reported racial differences in the presentation and outcome,
outcomes in the Swedish and Chinese
but little is known about differences between countries.
populations?

OBJECTIVE To compare preeclampsia prevalence, risk factors, and pregnancy outcomes between Findings In this cross-sectional study of
the Swedish and Chinese populations. 634 689 pregnancies, preeclampsia had
a similar prevalence in Sweden (2.8%)
DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study compared deliveries from the and China (2.2%), but two-thirds of
Swedish national Medical Birth Register (2007-2012) and the China Labor and Delivery Survey (2015- cases were mild in Sweden, while
2016). The Swedish Medical Birth Register records maternal, pregnancy, and neonatal information two-thirds of cases were severe in
for nearly all deliveries in Sweden. The China Labor and Delivery Survey was conducted throughout China, and notable differences were
China, and these data were reweighted to enable national comparisons. Participants included found for the association of nulliparity
555 446 deliveries from Sweden and 79 243 deliveries from China. Data management and analysis and body mass index. The stillbirth rate
was conducted from November 2018 to August 2020 and revised in February to March 2021. for preeclampsia in China was almost
10-fold higher than in Sweden.
EXPOSURES Maternal characteristics, parity, multiple gestation, chronic and gestational diabetes,
Meaning This comparison adds to the
cesarean delivery.
global literature on preeclampsia, helps
to fill the data gap for Asian populations,
MAIN OUTCOMES AND MEASURES Preeclampsia prevalence and risk factors, overall and for mild
and suggests an important role for the
and severe forms and rates of adverse neonatal outcomes compared with pregnancies with no
management of maternal care.
gestational hypertension.

RESULTS The 555 446 Swedish pregnancies and 79 243 Chinese pregnancies had mean (SD) + Supplemental content
maternal age of 30.9 (5.3) years and 28.6 (4.6) years, respectively. The overall prevalence of Author affiliations and article information are
preeclampsia was similar in Sweden and China, 16 068 (2.9%) and 1803 (2.3%), respectively, but listed at the end of this article.

with 5222 cases (32.5%) considered severe in Sweden and 1228 cases (68.1%) considered severe in
China. Obesity (defined as BMI ⱖ28 in China and BMI ⱖ30 in Sweden) was a stronger risk factor in
China compared with Sweden (China: odds ratio [OR], 5.12; 95% CI, 3.82-6.86; Sweden: OR, 3.49;
95% CI, 3.31-3.67). Nulliparity had a much stronger association with severe preeclampsia in Sweden
compared with China (Sweden: OR, 3.91; 95% CI, 3.65-4.18; China: OR, 1.65; 95% CI, 1.20-2.25). The
overall stillbirth rate for singleton in China was more than 3-fold higher than in Sweden (846/
77 512[1.1%] vs 1753/547 219 [0.3%], P < .001), and 10-fold higher among women with preeclampsia
(66/1652 [4.6%] vs 60/14 499[0.4%], P < .001).

CONCLUSIONS AND RELEVANCE In this study, the prevalence rates of preeclampsia in Sweden and
China were similar, but women in China had more severe disease and worse pregnancy outcomes
than women in Sweden. The associations of obesity and nulliparity with preeclampsia suggest a role
for lifestyle and health care factors but may reflect some differences in pathophysiology. These

(continued)

Open Access. This is an open access article distributed under the terms of the CC-BY License.

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Abstract (continued)

findings have relevance for current efforts to identify high-risk pregnancies and early serum markers
because the value of risk prediction models and biomarkers may be population specific.

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Introduction
Preeclampsia is a major maternal health issue worldwide that is responsible for maternal and
neonatal severe morbidity and mortality and has substantial contributions to prematurity of the fetus
and long-term cardiovascular disease (CVD) in the mother.1 Although the definition of preeclampsia
varies between countries, most are similar to the definition provided by the International Society for
the Study of Hypertension in Pregnancy (ISSHP),2,3 which is predominantly used worldwide. The
ISSHP defines preeclampsia as the presence of new-onset hypertension and proteinuria or other
end-organ damage occurring after 20 weeks of gestation,4 with eclampsia defined as the
development of grand seizures in a woman with preeclampsia. Preeclampsia affects an estimated
4.6% of pregnancies globally.5
The etiology of preeclampsia is complex, and a role for maternal and fetal and/or paternal
genetic determinants has been suggested by early family-based studies.6,7 The association of
ethnicity with preeclampsia severity has generally been investigated in within-country studies in
multicultural settings, comparing mostly African American, Hispanic, and White subgroups in the
United States.8,9 In addition to the sparsity of data about Asian or Chinese women as an ethnic
subgroup in those studies, there are no population-based studies of preeclampsia among women in
China. However, the many racial and ethnic differences that were noted in a recent review10 suggest
that there could be important differences between women in China and Europe. Ethnic differences
reflect many factors, such as lifestyle, socioeconomic status, cultural norms, and the seeking and
provision of medical care,11 which can have a greater association with differences between countries
than racial or genetic factors. However, genetic studies have suggested some association with
preeclampsia, including variations in MS-like tyrosine kinase 1 and vascular endothelial growth factor
C12 and a microsatellite variation in the heme-oxygenase 1promoter in a Finnish cohort13 but not in a
Chinese cohort.14 Thus, based on the various types of evidence available from current research and
the potential impact of health care infrastructure on diagnosis, management, and related
complications of preeclampsia, we hypothesized that the etiology, severity, and consequences of
preeclampsia may differ in a country-level comparison of China and Sweden.
The national registers that enable between-country comparisons of population health are
generally available in high-income countries, and it is rare to have country-level data for middle-
income countries. A systematic review of global burden of preeclampsia and eclampsia5 has
highlighted this gap in knowledge and the consequent need for more large surveys to obtain reliable
estimates and inform policy. The data from the China Labor and Delivery Survey (CLDS) conducted
throughout China15 offers a unique resource, which can be analyzed by inverse probability weighting
(IPW)15,16 to provide country-level estimates that enable the comparison of a middle-income country
with a high-income country. The present study uses 2 population-based data resources, the Swedish
Medical Birth Register (MBR) and the CLDS to compare the prevalence, risk factors, and pregnancy
outcomes for mild preeclampsia and severe preeclampsia between the 2 countries.

Methods
Study Populations
The MBR records maternal, pregnancy and neonatal information for nearly all deliveries in Sweden.
During the study period (2007-2012), the register included deliveries at 22 weeks gestation or

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more.17 From these deliveries, there were 555 446 records available for analysis after excluding
mothers with chronic hypertension.
In the CLDS, conducted from March 1, 2015 to December 31, 2016,15 information on more than
80 000 deliveries was extracted by trained research nurses in 89 hospitals from 24 of 34 provinces
and autonomous regions in China. In this study, we included a total of 79 243 deliveries of at least 22
weeks gestation to women without chronic hypertension.
Ethical approvals were obtained from the Stockholm Regional Ethics Committee and the Xinhua
Hospital Ethics Committee Affiliated to Shanghai Jiaotong University School of Medicine. The
deidentified linkage of the Swedish national register data did not require informed consent. Because
only anonymous clinical information was collected in the China Labor and Delivery Survey, no
individual informed consent was obtained.15 We followed the Strengthening the Reporting of
Observational Studies in Epidemiology (STROBE) reporting guideline.

Identification of Hypertensive Disorders in Pregnancy

In Sweden, preeclampsia was diagnosed by physicians according to the guidelines of the Swedish
Society of Obstetrics and Gynaecology18: mild preeclampsia was identified as gestational
hypertension with proteinuria (ⱖ300 mg/24 hours); if any of the 8 additional conditions in eTable 1
in the Supplement occurred, the preeclampsia was classified as severe. The diagnosis was recorded
as International Statistical Classification of Diseases and Related Health Problems, Tenth Revision
(ICD-10) codes in the MBR: gestational hypertension (ICD-10 code O13), mild preeclampsia (ICD-10
code O14.0), severe preeclampsia (ICD-10 codes O14.1 and O14.9), hemolysis, elevated liver enzymes,
low platelet count (HELLP) syndrome (ICD-10 code O14.2), or eclampsia (ICD-10 code O15). The
diagnosis criteria in the Chinese data set followed the guidelines of the Chinese Society of Obstetrics
and Gynecology19 with almost identical definitions as Sweden (eTable 1 in the Supplement), except
for some additional conditions for classifying the diagnosis as severe. We classified pregnancies from
both countries into 3 groups: no gestational hypertension (as the reference), mild preeclampsia, and
severe preeclampsia. HELLP syndrome and eclampsia were included in the severe preeclampsia
group. If more than 1 hypertensive disorder was registered, the pregnancy was classified according
to the most severe diagnosis.

Identification of Adverse Pregnancy Outcomes

Live births before 37 completed weeks were classified as preterm, according to the World Health
Organization (WHO) definition.20 All pregnancies were classified according to whether they resulted
in a liveborn or stillborn neonate. A 5-minute Apgar score of less than 7 was defined as low.21 Birth
weights less than 500 g or greater than 7000 g were considered unknown.

Definition of Potential Risk Factors

Maternal body mass index (BMI; calculated as weight in kilograms divided by height in meters
squared) was calculated at first prenatal care visit in Sweden and classified using the WHO
definition22(underweight, <18.5; reference weight, 18.5-24.9; overweight, 25.0-29.9; obese, ⱖ30.0).
In China, prepregnancy BMI was categorized using the Chinese cutoffs, which are slightly different
than the WHO definition23 (underweight, <18.5; reference weight, 18.5-23.9; overweight, 24-27.9;
obese, ⱖ28). Binary (yes or no) risk factors included advanced maternal age (ⱖ35 years at delivery),
parous or nulliparous, multiple gestation, history of diabetes, and gestational diabetes (Table 1).

Statistical Analysis
Descriptive comparisons between Sweden and China used χ2 tests for categorical variables and
student t tests for continuous variables. The Chinese multilevel survey recorded pregnancies within
hospitals and provinces. Because population and hospital statistics were available, the overall
epidemiology of preeclampsia in China can be represented by the application of IPW to this complex
survey data.24 The proportion of participating hospitals in each province, representing the

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probability that a hospital was represented in the survey, was calculated separately for secondary and
tertiary hospitals, using the numbers of hospitals in each province in 2016.25 Because, each hospital
contributed all their delivery records for a specified period, these were assumed to be a
representative proportion of the annual number of births in the hospital in 2016.15 The inverse of the
product of these 2 proportions and probabilities provides the appropriate weight for an IPW analysis
to obtain population estimates.
Univariable and multivariable logistic regression models were used to estimate the crude and
adjusted odds ratios (ORs) for the association between potential risk factors and preeclampsia, with
weighted logistic models used for the Chinese data. For the univariable regression model, any
variable statistically significant in either country was reported (Table 2). Because maternal age,
maternal BMI, parity, multiple gestation, history of diabetes, and gestational diabetes have been
previously reported and have been validated as clinical risk factors for preeclampsia,26 these factors
were all adjusted for in the multivariable regression models, regardless of statistical significance. For

Table 1. Overall Demographic Description of the Pregnant Women in the Swedish and Chinese Populationsa

No. (%)
Characteristic Sweden China P value
No. 555 446 79 243
Age, y
Mean (SD) 30.91 (5.25) 28.63 (4.61) <.001
<35 445 615 (80.2) 70 242 (88.9)
<.001
≥35 109 831 (19.8) 9001 (11.1)
Prepregnancy
BMI, mean (SD) 24.62 (4.47) 21.87 (3.29) <.001b
Underweight 12 685 (2.3) 7163 (11.6)
Reference weight 321 441 (57.9) 38 051 (66.6)
Overweight 133 416 (24.0) 9931 (17.2) <.001c
Obesity 63 846 (11.5) 2693 (4.6)
Missing 24 058 (4.3) 21 405 (27.0)c
Parity <.001
Nulliparous 244 417 (44.0) 44 250 (54.3)
Parous 311 029 (56.0) 34 5915 (45.7)
Multiple gestation
Yes 7578 (1.4) 1733 (1.8) <.001
No 547 868 (98.6) 77 510 (98.2)
History of diabetes
Yes 3190 (0.6) 816 (0.8) <.001
No 552 256 (99.4) 77 996 (99.2)
Gestational diabetes
Yes 5692 (1.0) 7799 (9.8) <.001b
No 549 754 (99.0) 70 349 (88.8)
Missingc NA 1095 (1.4)
Cesarean delivery
Yes 95 091(17.1) 29 124 (34.5) <.001
No 460 355 (82.9) 49 781 (65.5) Abbreviations: BMI, body mass index calculated as
Hypertensive disorders in pregnancy weight in kilograms divided by height in meters
Total 22 089 (3.98) 3383 (4.02) squared; NA, not applicable.
a
Gestational hypertension 6021 (1.1) 1580 (1.8) Values for China are presented as observed mean
(SD) or observed/unweighted No. (weighted %).
Preeclampsia .002
b
χ2 test of nonmissing categories.
Mild 10 138 (63.1) 575 (31.9)
c
Severe 5222 (32.5) 1228 (68.1) The percentage of missing vales was 1.4% for
gestational diabetes and 27% for BMI, all other
Unspecified 708 (4.4) NA
variables were at least 99.5% complete.

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the separate analysis of mild preeclampsia and severe preeclampsia, the adjusted ORs with 95% CIs
are presented on forest plots.
The rates of preterm birth, low birth weight, and low 5-min Apgar score for pregnancies with
mild and severe preeclampsia are illustrated using bar charts, and the Swedish and Chinese rates
compared using (weighted) χ2 tests. Stillbirth rates are presented and tested for all women with
preeclampsia (whether mild or severe) because all preeclamptic pregnancies resulting in stillbirth are
coded as severe by the Chinese guidelines.19 Data management and analysis were conducted using
SAS statistical analysis software, version 9.4 (SAS Institute, Inc), and figures were prepared using R
statistical software, version 3.4.1 (R Project for Statistical Computing). A 2-sided P < .05 was
considered statistically significant.

Results
Descriptive Results
A total of 555 446 and 79 243 pregnancies were extracted from the Swedish Medical Birth Register
and the China Labor and Delivery survey, respectively, with 22 089 (3.98%) and 3383 (4.27%) having
a diagnosis of gestational hypertension (Figure 1). Of our sample, 76 315 (95) Chinese mothers were
Han. The Swedish data recorded only maternal country of birth and not ethnic background (which
may be mixed), and therefore the ethnic makeup of the sample could not be assessed. The mean
(SD) maternal age was higher in mothers from Sweden than mothers from China (30.9 [5.6] years vs
28.6 [4.6] years). The mean (SD) BMI was also higher in mothers from Sweden than mothers from
China (24.6 [4.5] vs 21.9 [3.3]). The obesity rate in Sweden was more than double the rate in China
(63 846 [11.5%] vs 2693 [4.6%]) (Table 1). There were 244 417 first deliveries (44.0%) in Sweden and
44 250 (54.3%) in China.

Table 2. Crude OR (95% CI) From Logistic Regression Analysis

Preeclampsia, crude OR (95% CI)

Mild Severe
Variable Sweden Chinaa Sweden Chinaa
Maternal age at delivery ≥35 1.07 (1.02-1.13) 2.06 (1.22-3.48) 1.14 (1.06-1.22) 2.04 (1.59-2.63)
BMIb
Underweight 0.76 (0.63-0.91) 0.41 (0.18-0.92) 0.78 (0.62-0.99) 0.66 (0.45-0.95)
Overweight 1.71 (1.63-1.80) 3.14 (1.98-4.99) 1.35 (1.26-1.45) 2.29 (1.59-3.30)
Obese 3.23 (3.07-3.40) 4.86 (3.64-6.51) 2.10 (1.94-2.27) 4.46 (3.27-6.07) Abbreviations: BMI, body mass index calculated as
weight in kilograms divided by height in meters
Nulliparous 2.49 (2.39-2.59) 1.40 (0.88-2.22) 3.31 (3.10-3.53) 1.20 (0.92-1.55)
squared; OR, odds ratio.
Multiple gestation 4.42 (4.04-4.85) 2.57 (1.49-4.46) 5.76 (5.12-6.47) 6.21 (4.60-8.38) a
Results for China are from weighted logistic
History of diabetes 4.62 (4.04-5.29) 1.31 (0.59-2.90) 5.36 (4.47-6.43) 3.15 (1.37-7.27)
regression.
Gestational diabetes 2.97 (2.63-3.35) 1.23 (0.80-1.91) 2.29 (1.88-2.80) 2.13 (1.58-2.87) b
Reference group: normal BMI.

Figure 1. Flowchart of the Study Population in Sweden and Surveyed Sample in China

Sweden China

555 446 Pregnancies included from Swedish 79 243 Pregnancies included from China Labor
Medical Birth Register, 2007-2012 and Delivery Survey, 2015-2016

533 357 Without hypertensive 22 089 Hypertensive disorders 75 860 Without hypertensive 3383 Hypertensive disorders
disorders in pregnancy in pregnancy disorders in pregnancy in pregnancy
10 138 Mild preeclampsia 1580 Gestational hypertension
6021 Gestational hypertension 1228 Severe preeclampsia
5222 Severe preeclampsia 575 Mild preeclampsia
708 Unspecified preeclampsia

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The prevalence of chronic diabetes and gestational diabetes were both significantly higher in
China than in Sweden (chronic diabetes: 816 [0.8%] vs 3190 [0.6], P < .001; gestational diabetes:
7799 [8.4%] vs 5692 [1.0%], P < .001. The multiple gestation rate was similar in the 2 countries
(7578 [1.4%] in Sweden and 1733 [1.8%] in China), and women who were nulliparous accounted for
approximately half the deliveries in both countries (244 417 [44.0%] in Sweden vs 44 250 [54.3%] in
China). More cesarean deliveries were performed in China than in Sweden (29 124 [34.5%] vs
95 091 [17.1%]).
The overall prevalence of preeclampsia was similar in Sweden and China, 16 068 (2.9%) and
1803 (2.3%), respectively. The overall prevalence of hypertensive disorders was almost identical in
Sweden and China (22 089 [3.98%] and 3383 [4.02%]). However, there was a significant difference
in the proportions of mild and severe preeclampsia. Of all preeclampsia cases, mild preeclampsia
was more prevalent in Sweden than in China (10 138 [63.1%] vs 575 [31.9%]), while severe
preeclampsia was less prevalent in Sweden (5222 [32.5%] vs 1228 [68.1%] in China; P < .001).

Risk Factors for Preeclampsia

Table 2 presents crude ORs for the association of risk factors with preeclampsia. Maternal age of 35
years or older was significantly associated with both mild and severe preeclampsia in Sweden and
China (mild: OR, 1.07; 95% CI, 1.02-1.13 and OR, 2.06; 95% CI, 1.22-3.48; severe: OR, 1.14; 95% CI,
1.06-1.22 and OR, 2.04; 95% CI, 1.59-2.63). Multiple gestation was significantly associated with both
mild and severe preeclampsia in Sweden and China (mild: OR, 4.42; 95% CI, 4.04-4.85 and OR, 2.57;
95% CI, 1.49-4.46; severe: OR, 5.76; 95% CI, 5.12-6.47 and 95% CI, 6.21; OR, 4.60-8.38). Having
overweight was significantly associated with both mild and severe preeclampsia in Sweden and
China (mild: OR, 1.71; 95% CI, 1.63-1.80 and OR, 3.14; 95% CI, 1.98-4.99; severe: OR, 1.35; 95% CI,
1.26-1.45 and OR, 2.29; 95% CI, 1.59-3.30). Having obesity was significantly associated with both mild
and severe preeclampsia in Sweden and China (mild: OR, 3.23; 95% CI, 3.07-3.40 and OR, 4.86; 95%
CI, 3.64-6.51; severe: OR, 2.10; 95% CI, 1.94-2.27 and OR, 4.46; 95% CI, 3.27-6.07). In Sweden, a
significantly higher risk of mild and severe preeclampsia was associated with nulliparity, history of
diabetes, and gestational diabetes (nulliparity: OR, 2.49; 95% CI, 2.39-2.59 and OR, 3.31; 95% CI,
3.10-3.53; history of diabetes: OR, 4.62; 95% CI, 4.04-5.29 and OR, 5.36; 95% CI, 4.47-6.43; and
gestational diabetes: OR, 2.97; 95% CI, 2.63-3.35 and OR, 2.29; 95% CI, 1.88-2.80). In China there
was no significant association with parity, and diabetes was only associated with the risk of severe
preeclampsia (history of diabetes: OR, 3.15; 95% CI, 1.37-7.27 and gestational diabetes: OR, 2.13; 95%
CI, 1.58-2.87).
The adjusted ORs (aORs) and 95% CIs are presented in Figure 2 (eTable 2 in the Supplement).
Maternal age of 35 years or older had a weaker association with mild and severe preeclampsia in
Sweden than in China (mild: aOR, 1.31; 95% CI 1.24-1.38 vs aOR, 2.15; 95% CI, 1.50-3.08; severe: aOR,
1.50; 95% CI, 1.39-1.62 vs aOR, 1.87; 95% CI, 1.44-2.43).
Women in China who had overweight or obesity had a 3-fold risk and 5-fold risk of mild
preeclampsia (OR, 3.20; 95% CI, 2.02-5.06 and OR, 5.12; 95% CI, 3.82-6.86) and a 2-fold and 4-fold
risk of severe preeclampsia (OR, 2.12; 95% CI, 1.49-3.03 and OR, 4.01; 95% CI; 2.96-5.43) compared
with women with reference weight. All of the associations with overweight and obesity were
stronger in women in China than women in Sweden.
Women in Sweden who were nulliparous had a 3- and 4-fold higher risk of mild and severe
preeclampsia (OR, 2.97; 95% CI, 2.84-3.10 and OR, 3.91; 95% CI, 3.65-4.18), which were higher than
the relative risks for women in China. Multiple gestation was associated with at least a 4-fold
increased risk of severe preeclampsia in Sweden and China (OR, 5.78; 95% CI, 5.11-6.54 and OR 4.11,
95% CI, 3.30-5.12) and with mild preeclampsia in Sweden (OR 4.52, 95% CI, 4.11-4.97).
A history of diabetes was associated with mild preeclampsia and severe preeclampsia in
Sweden (OR, 3.90; 95% CI, 3.38-4.49 and OR, 5.06; 95% CI, 4.19-6.12), while in China there was no
association with mild preeclampsia and a weak association with severe preeclampsia (OR, 0.51; 95%
CI, 0.19-1.37 and OR, 1.68; 95% CI, 1.19-2.35). In Sweden, associations with gestational diabetes were

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weaker than with having a history of diabetes but still significant, while in China the associations were
of similar magnitude to those for chronic diabetes and only significant for severe preeclampsia
(eTable 2 in the Supplement).

Pregnancy Outcomes
The neonatal outcomes for singleton pregnancies were significantly different between the 2
countries and are presented in eTable 3 in the Supplement. China had higher overall rates of stillbirth
than Sweden (846 [1.1%] vs 1753 [0.3%]), preterm birth (6157 [6.7%] vs 24 870 [4.5%]) and low birth
weight (4105 [4.6%] vs 15 710 [2.9%]), while the prevalence of low 5-minute Apgar score was
somewhat lower (801 [1.0%] vs 6889 [1.3%]). Mean gestational age at delivery and birth weight
were significantly higher in Sweden (median [interquartile range, IQR], 40 [39.0-41.0] wk vs 39.0
[38.0-40.0] wk, and median [IQR], 3555 [3220-3890] g vs 3300 [3000-3600] g). All comparisons
were significant at P < .001.
Figure 3 presents a comparison of singleton pregnancy outcomes in Sweden and China, for
pregnancies with no gestational hypertension, mild preeclampsia, and severe preeclampsia (eTable 4
in the Supplement). Multiple pregnancies are not presented because of insufficient data. The
stillbirth rate for singleton pregnancies complicated by preeclampsia was 66 of 1652 (4.6%) in the
Chinese survey data, 10-fold higher than in Sweden (60/14 499; 0.4%). A low 5-minute Apgar score
was associated with both mild and severe preeclampsia in Sweden but only with severe preeclampsia
in China, where it was of much larger magnitude than Sweden.
Both Sweden and China had an increasing rate of low birth weight and preterm birth rate across
the 3 categories of exposure (no gestational hypertension, mild preeclampsia, severe preeclampsia).
The proportions of low birth weights were similar in Sweden and China, with 916 (9.5%) and 50
(10.1%) in the mild preeclampsia group and 1821 (37.5%) and 453 (37.1%) in the severe group. The

Figure 2. Adjusted Odds Ratios for Risk Factors Associated With Mild Preeclampsia and Severe Preeclampsia From Multivariable Logistic Regression for Sweden
and Weighted Logistic Regression for China

Mild preeclampsia Favors no mild Favors mild Severe preeclampsia Favors no severe Favors severe
Variable OR (95% CI) preeclampsia preeclampsia P value OR (95% CI) preeclampsia preeclampsia P value
Maternal age: ≥35 vs <35
Sweden 1.31 (1.24-1.38) <.001 1.50 (1.39-1.62) <.001
China 2.15 (1.50-3.08) <.001 1.87 (1.44-2.43) <.001
BMI: underweight vs normal
Sweden 0.73 (0.61-0.87) <.001 0.75 (0.59-0.96) <.001
China 0.41 (0.18-0.91) .03 0.68 (0.46-0.99) .05
BMI: overweight vs normal
Sweden 1.81 (1.72-1.90) <.001 1.44 (1.35-1.55) <.001
China 3.20 (2.02-5.06) <.001 2.12 (1.49-3.03) <.001
BMI: obesity vs normal
Sweden 3.49 (3.31-3.67) <.001 2.31 (2.13-2.50) <.001
China 5.12 (3.82-6.86) <.001 4.01 (2.96-5.43) <.001
Parity: 1 vs ≥2
Sweden 2.97 (2.84-3.10) <.001 3.91 (3.65-4.18) <.001
China 2.11 (1.37-3.26) .001 1.65 (1.20-2.25) .002
Multiple gestation: yes vs no
Sweden 4.52 (4.11-4.97) <.001 5.78 (5.11-6.54) <.001
China 2.33 (1.28-4.25) .007 4.11 (3.30-5.12) <.001
History of diabetes: yes vs no
Sweden 3.90 (3.38-4.49) <.001 5.06 (4.19-6.12) <.001
China 0.51 (0.19-1.37) .18 1.68 (1.19-2.35) .004
Gestational diabetes: yes vs no
Sweden 1.90 (1.67-2.17) <.001 1.62 (1.31-2.01) <.001
China 0.73 (0.47-1.13) .16 1.57 (1.14-2.16) .006

0.1 1 7 0.1 1 7
Mild preeclampsia Severe preeclampsia
OR (95% CI) OR (95% CI)

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preterm rate in Sweden was significantly lower than China for mild preeclampsia, 812 (8.5%) vs 77
(12.8%), and significantly higher for severe preeclampsia, 2,094 (42.8%) vs 515 (37.9), with P < .001
for both comparisons.

Discussion
Our results highlight several differences between Sweden and China regarding the presentation and
risk factors of preeclampsia and the outcomes of affected pregnancies. The overall prevalence of
gestational hypertensive disorders was approximately 4% in both countries, but the ratio between
mild and severe preeclampsia was reversed: two-thirds of the cases were mild in Sweden, while
two-thirds of the cases were severe in China. We found notable differences in the associations with
known risk factors in the 2 populations: maternal age and obesity had a milder association in Sweden,
while in China, obesity was associated with a 4- to 5- fold increased risk; nulliparity was a risk factor
in both populations, but with a much stronger association in Sweden. The stillbirth rate for singleton
pregnancies in the overall surveyed population was 1.1% in China, which was more than 3 times as
high as in Sweden (0.3%). For pregnancies complicated by preeclampsia, the risk of stillbirth in
women in China was 4.6% while it was only 0.4% in Sweden.
Multiple gestation, which was a strong risk factor in both countries, is a known risk factor for
preeclampsia, with a 2-fold increased risk reported in United States populations of Black women and

Figure 3. Comparison of Adverse Outcomes of Singleton Pregnancies Associated With Preeclampsia in Sweden and China

A Stillbirth rate B Apgar score

7 7
P <.19
Country
6 6
Rate of low 5 min Apgar score, %

Sweden China

5 P <.001 5
Stillbirth rate, %

4 4

3 3
P <.001

2 2
P <.001
P <.001
1 1

0 0
None Preeclampsia None Mild preeclampsia Severe preeclampsia
Hypertensive disorders in pregnancy Hypertensive disorders in pregnancy

C Preterm birth D Low birth weight

50 50
P <.001

P = .55
40 40
Low birth weight rate, %
Preterm birth rate, %

30 30

20 20
P <.001
P = .05
10 P <.001 10
P <.001

0 0
None Mild preeclampsia Severe preeclampsia None Mild preeclampsia Severe preeclampsia
Hypertensive disorders in pregnancy Hypertensive disorders in pregnancy

Pregnancies with no gestational hypertension are included as reference.

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White women.27 In our study, the larger odds ratios of 4 to 5 in Sweden are consistent with a 4-fold
increase in Norway.28
Ethnicity has previously been suggested as a risk factor for preeclampsia in a study within
China29 and may explain some of the differences with Sweden. However, China has a significant Han
majority (approximately 92% of the population), while Sweden is less homogenous, with
approximately 80% of the population born in Sweden, and many of those may have a mixed ethnic
background. There are many aspects of ethnicity, such as lifestyle, diet, and the seeking and provision
of health care, that are likely to be more strongly associated with preeclampsia risk than the racial or
genetic background. For example, in our study, obesity was a much stronger risk factor for women in
China. Increased risks of 2- to 3-fold have been reported for non-Hispanic White or non-Hispanic
Black women with obesity.30,31 Furthermore, a meta-analysis32of White populations from North
America or Europe reported a relative risk of 4.14 (95% CI, 3.61-4.75) for risk of preeclampsia in
women with BMI of more than 35 compared with a BMI of less than 25.
Several metabolic perturbations have been suggested as responsible for the association
between obesity and preeclampsia, such as elevated leptin, proinflammatory status, or dysfunction
of the nitric oxide synthase system.33 Our findings show that the risk of preeclampsia for women in
China rises more rapidly with BMI than for Swedish women. The recording of prepegnancy BMI in
China and the BMI in Sweden at the first prenatal visit is unlikely to explain much of this difference
because we would not expect much change in this period.34 One hypothesis is that metabolic
perturbations may appear earlier with increased BMI in Asian women, who have higher levels of
visceral adiposity,35 which is associated with cardiovascular and metabolic disease.36
The high stillbirth rate in the overall Chinese population is consistent with the literature37 and
more than 3 times as high as the stillbirth rate in Sweden. Worldwide, stillbirth rates are difficult to
assess, as this indicator was not part of the WHO Millennium Development Goals and therefore not
recorded in several countries, remaining an invisible aspect of adverse pregnancy outcome.38
Instead, the neonatal mortality rate is used for between-country comparisons, and huge disparities
are observed.38 Our data, which was from 1 high-income and 1 middle-income country, reflects only a
small part of this variation. However, it is compelling to observe that the risk of stillbirth was higher
in women in China with preeclampsia (4.6%) than in the general population (1.1%), while in Sweden
the rate only increased from 0.3% to 0.4%. Increased adverse outcomes, including stillbirths, have
been reported for low- and middle-income countries,39 and the magnitude of the difference we
observed between Sweden and China is more likely because of cultural and health care factors11 than
genetic variation. We considered a number of potential explanations for the differences, including
the protocols for antenatal care, association of prematurity with stillbirth risk, and duration of
in-hospital care. The management of maternal health care in China or the care-seeking behavior of
pregnant women might result in preeclampsia not being identified until symptoms have become
more severe. The typical schedule for routine prenatal follow-up in both countries includes 4 visits up
to week 32: following this, China has 2 visits in weeks 33 to 36 and 37 to 41, while Sweden has visits
every second week until delivery.40 Thus, women in China have less surveillance in late pregnancy,
when preeclampsia onset is more likely. Differences in health care are also evident from the high
overall cesarean delivery rate (34.5%) in China (double that of Sweden’s 17.1%) which is consistent
with other studies.41,42
The management of preeclampsia before gestational week 37 is challenging in low- and middle-
income countries.39 To accommodate the WHO definition of stillbirth,43 we stratified by gestational
age at delivery (<28 weeks, 28-31 weeks, 32-36 weeks, and ⱖ37 weeks). Among extremely preterm
deliveries (<28 weeks), the stillbirth rate was 16.5% in Sweden and 80% in China, and among very
preterm (28-31 weeks), it was 1.3% and 28%. The stillbirth rate was low in both countries for full-term
deliveries, but there was still a 4-fold difference (0.11% in Sweden vs 0.48% in China). We
hypothesized that women in China may seek medical help later, with a result that intrauterine death
has already occurred when they arrive at the hospital. However, 33 of 45 extremely and very preterm
deliveries (73.3%) were more than 24 hours after hospitalization, suggesting that the fetus was alive

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when the woman reached maternity care. Thus, the high stillbirth rates are more likely to be due to
aspects of expectant care44 combined with unexpected complications. The contribution of maternal
factors and surveillance protocols is an important area for further investigation.
Regarding genetic factors, it has long been known that there is familial clustering of
preeclampsia,7 and more recently, discoveries of genetic markers associated with plausible biological
angiogenic pathways have been made.12,45 Asian and women in China have been underrepresented
in genetic studies of preeclampsia. Our work provides a comparison of an Asian and a European
country that are not genetically homogenous populations, but our results nonetheless suggest that
genetic studies focused on ethnic Chinese women could provide important insights. Additional
population-based epidemiological studies, such as comparing women in China with their migrant
counterparts, could also help to unravel the genetic and environmental contributions to
preeclampsia risk.
A strength of this study is the availability of representative population data in a high-income and
middle-income country, enabling a between-country comparison and a contribution to the global
depiction of preeclampsia. The MBR captures almost every birth in Sweden using ICD codes that have
been reported to have high validity for identifying preeclampsia (positive predictive value of 92.6%)
in the Swedish context.46
The participating provinces in the CLDS represent 92% of the population (and 89% of the
births) during the years of the survey. Thus, our weighted estimates represent most of the Chinese
population. By taking account of the numbers and sizes of secondary and tertiary hospitals in the
weighted analysis, we mitigated the potential bias from referral patterns or participation rates in
the survey.

Limitations
This study has limitations. Although almost identical diagnosis criteria were used for mild
preeclampsia in the 2 countries, the Chinese definition included some additional criteria for the
classification of the condition as severe (eTable 1 in the Supplement). Most of these additional criteria
are too rare to explain the higher prevalence of severe preeclampsia, but fetal growth restriction is
relatively common, and its strong association with preeclampsia47 may have resulted in some
diagnostic or misclassification bias.
The numbers of study mothers from the 2 countries were unbalanced, with the Chinese survey
sample being approximately 14% of the Swedish study population. Despite the smaller sample size,
the Chinese data provided estimates with good precision and had sufficient statistical power to
identify important differences with Sweden.
Although the Swedish prevalence is for a time (2007-2012) when preeclampsia rates were
shown to be stable by our group (eFigure in the Supplement) and others,48 we cannot exclude the
possibility of confounding by unmeasured factors during this 6-year period. The Chinese prevalence
is estimated during 2015 to 2016, so any comparison with Sweden during the same calendar year(s)
would require the assumption that the Swedish rates do not change substantially for a further 3 to 4
years. Interestingly, the 2015 to 2016 prevalence in China was remarkably close to that of Sweden
during a 6-year period. Given this similarity, an interesting area for further investigation is whether
the proportion of severe disease and associated adverse outcomes in China have reduced in
recent years.
A major limitation of our study is the lack of information about differences in the management
of preeclampsia. There were also no details about treatment available for either country. A further
limitation of the data from both countries is that the date of preeclampsia onset or diagnosis was not
available, so that we were unable to separate early and late-onset preeclampsia.
While our study is nationally representative, we do not have the necessary information to
estimate the association with ethnic or genetic factors. Although 95% of the Chinese survey sample
were Han women (similar to 92% nationally), we cannot assume our results apply to this ethnic
group without having the population and hospital statistics stratified by ethnic group for the IPW

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 JAMA Network Open | Obstetrics and Gynecology Preeclampsia Prevalence, Risk Factors, and Pregnancy Outcomes in Sweden and China

estimation. The Swedish data records maternal country of birth, not ethnic background (which may
be mixed), so these data can only be interpreted as representative of a country and not of one or
more ethnic groups.

Conclusions
In this study, important differences were found between women in Sweden and China in the overall
rate of severe preeclampsia, the contributions of risk factors, and the fetal outcomes for affected
pregnancies. While the differences in the association with parity and BMI are likely because of ethnic
and social factors, the higher prevalence of severe disease and rate of adverse pregnancy outcomes
in China may reflect differences in national protocols for antenatal care and the management of
pregnancies that are complicated by preeclampsia. An underlying genetic association or potential
difference in pathophysiology between Chinese and European women cannot be ruled out. Variation
in the contributions of risk factors across populations could be important for global efforts to identify
early serum markers of preeclampsia and also have consequences for the development of complex
prediction models for pregnancies at risk of preeclampsia.49,50 Our work suggests that comparative
studies of preeclampsia need to consider diagnostic differences, social and ethnic factors, and
various aspects of health care protocols. While this study has highlighted the potential importance of
national health care protocols in comparing different countries, differences in health care may also
be important in the interpretation of findings from within-country studies of multiethnic
populations.

ARTICLE INFORMATION
Accepted for Publication: March 10, 2021.
Published: May 10, 2021. doi:10.1001/jamanetworkopen.2021.8401
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Yang Y et al.
JAMA Network Open.
Corresponding Authors: Marie Reilly, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska
Institutet, Nobel’s vag 12A, 171 77 Stockholm, Sweden (marie.reilly@ki.se); Jing Hua, MD, PhD, Department of
Women and Children’s Health Care, Shanghai First Maternity and Infant Hospital, Tongji University School of
Medicine, West Gaoke Road 2699, 201204 Shanghai, China (huajing_mih@163.com).
Author Affiliations: Department of Women and Children’s Health Care, Shanghai First Maternity and Infant
Hospital, Tongji University School of Medicine, Shanghai, China (Yang, Hua); Department of Medical Epidemiology
and Biostatistics, Karolinska Institute, Stockholm, Sweden (Yang, Le Ray, Reilly); Department of Gynecology and
Obstetrics, Strasbourg University Hospital, Strasbourg, France (Le Ray); Ministry of Education-Shanghai Key
Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of
Medicine, Shanghai, China (Zhu, Zhang); Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai
Jiao Tong University School of Medicine, Shanghai, China (Zhu).
Author Contributions: Drs Reilly and Yang had full access to all of the data in the study and take responsibility for
the integrity of the data and the accuracy of the data analysis.
Concept and design: Yang, Le Ray, Hua, Reilly.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Yang, Reilly.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Yang, Reilly.
Obtained funding: Yang, Reilly.
Administrative, technical, or material support: Yang, Zhu, Zhang, Hua, Reilly.
Supervision: Le Ray, Hua, Reilly.
Conflict of Interest Disclosures: No disclosures were reported.

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 JAMA Network Open | Obstetrics and Gynecology Preeclampsia Prevalence, Risk Factors, and Pregnancy Outcomes in Sweden and China

Funding/Support: Dr Yang was supported by award No. 201808310056 from the China Scholarship Council and
grant No. 20174Y0010 from the Shanghai Municipal Commission of Health and Family Planning. Dr Reilly was
supported by contract No. 2016-02287_3 from the Swedish Science Council (Vetenskapsrådet).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and
decision to submit the manuscript for publication.
Additional Contributions: We thank Chen Wang, MSc, and Shengxin Liu, MSc, from Karolinska Institutet for help
with data management and analysis. We are grateful to Yilin Ning, PhD of Duke-National University of Singapore
Medical School for assistance with the figures. None of the contributors received compensation for their time.

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SUPPLEMENT.
eTable 1. Summary of Chinese Hypertensive Disorders in Pregnancy Guidelines (2015 Edition) and Translated
Guidelines From the Swedish Society of Obstetrics and Gynecology
eTable 2. Adjusted Odds Ratios From Multivariable Logistic Regression Model
eTable 3. Neonatal Outcomes of Singleton Pregnancies in Sweden and China
eTable 4. Comparison of Pregnancy Outcomes Among Singleton Pregnancies in Sweden and China
eFigure. Annual Prevalence of Hypertensive Disorders in Pregnancy in Sweden from 2002 to 2012

JAMA Network Open. 2021;4(5):e218401. doi:10.1001/jamanetworkopen.2021.8401 (Reprinted) May 10, 2021 14/14

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