Background
Hypertensive disorders of pregnancy (HDP) is one of the leading causes of maternal and fetal morbidity and mortality worldwide and potentially a critical threat to maternal and infant health [
1]. In 2013, the American Congress of Obstetricians and Gynecologists guidelines on hypertensive disorders complicating pregnancy generally classified HDP into four categories: gestational hypertension, preeclampsia/eclampsia, chronic hypertension, and chronic hypertension complicated with preeclampsia/eclampsia [
2]. As HDP is considered associated with cardiovascular diseases, the 2020 International Society of Hypertension guidelines continue the framework of the four-category HDP classification scheme, where hemolytic anemia, elevated liver enzymes and low platelet count syndrome (HELLP syndrome) are classified in a separate category [
3]. Regardless of how HDP is classified, the importance of blood pressure monitoring during pregnancy is emphasized.
Recent evidence has indicated an increase in the incidence rate of HDP over the past few decades, [
7,
8] suggesting that HDP, a sex-specific cardiovascular disease, will become increasingly important in the future [
4]. Although the importance of HDP in risk assessment and prevention programs has been recognized, the epidemiology of HDP is not well understood, especially in less developed countries, which may be an obstacle to HDP prevention and proper gestational healthcare strategies. The incidence of HDP ranges from 4 to 25 %, [
4,
5] and HDP is one of the three leading causes of maternal morbidity and mortality worldwide. In the past half century, the incidence of preeclampsia and maternal mortality has decreased significantly in developed countries. However, in developing countries, the incidence rates of preeclampsia and maternal mortality are still very high [
6]. According to the results of a meta-analysis, the global incidence of preeclampsia is 4.6 % [95 % confidence interval (CI), 2.7–8.2], which varies among different regions, such as 1.0 % in the eastern Mediterranean and 5.6 % in Africa [
6]. The incidence of preeclampsia also varies among different countries and regions, and thus the disease burden of HDP is difficult to estimate and HDP prevention is difficult among pregnant women globally [
7‐
11].
In recent years, the burden of HDP has been presented in some review papers based on a few national studies, but no detailed information from all countries has been provided. The overall aim of this study was to determine the epidemiological characteristics of HDP in a population-based cohort. This study presents the modeled global-, regional- and national-level prevalence and incidence rates, mortality rates and years lived with disability (YLDs) of HDP as revealed in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 and analyzes the associations between epidemiological data and socioeconomic factors, such as the sociodemographic index (SDI) and human development index (HDI), to provide comprehensive, comparable and up to date information on the HDP burden.
Discussion
As HDP is considered one of the major causes of maternal mortality worldwide, epidemiological surveillance of HDP is critical to gestational healthcare [
15]. To the best of our knowledge, this study is the first to analyze the trends in the HDP incidence at the global, regional and national levels and to examine the associations of the ASR of and EAPC in HDP with SDI and HDI in different countries or regions. From 1990 to 2019, the ASIR of HDPs decreased by an annual average of 0.68 %, while the total number of incident cases increased by 10.92 %. This pattern appears to suggest a major public health problem, as the ASIR has not substantially improved. The number of incident cases increased, probably due to population growth and multiple gestations. Notably, although the number of incident cases of HDP increased from 1990 to 2019, the incidence rate showed a decreasing trend, which was related to the increase in the global population. Moreover, both the number of deaths due to and ASDR of HDPs showed decreasing trends, which may be due to the advances medical interventions and gradually increasing attention to HDPs by clinicians worldwide [
7].
Socioeconomic status is associated with several diseases, such as neurological and immunorelated diseases [
16]. Obstetricians have known for many years that women with HDP generally have low total family incomes because the mortality rate of HDP is inversely correlated with average family income and maternal deaths from HDP/eclampsia are highest in areas of poverty [
17]. According to a previous study, the incidence of HDP varies according to family income. When grouped by income, the highest incidence rates of preeclampsia are observed in upper middle-income countries, whereas eclampsia appears to be more frequent in lower middle-income countries [
6]. In our study, both the incident case numbers and rates were highest in the low-SDI areas. At the national level, HDP incidence also showed a decreasing trend as SDI increased. A similar trend was also observed between ASIR and HDI, indicating important roles of economic support in gestational healthcare for both pregnant women and fetuses.
Previous studies reported that the risk of preeclampsia increased in an approximately linear manner with maternal age and that this pattern was similar in nulliparous and multiparous women [
18]. Luo et al. identified the incidence rates of pregnancy complications in nulliparous and multiparous Chinese women of advanced maternal age using a community-based prospective cohort. The findings suggested that women of advanced maternal age should be regarded as at high risk for pregnancy complications, including HDP [
19]. A large cohort of Japanese women with singleton pregnancies also indicated that advanced maternal age was a risk factor for HDP [
10]. Surprisingly, according to GBD database information, the incidence rate of HDP was highest in the group aged 25–29 years in our study, because the population included in the calculation comprised all women in that age group, not only pregnant women. This phenomenon was also observed in the GBD-based “Maternal Health Report” (
https://maternalhealthatlas.org/) [
20]. However, when using the fertility rate and other information to estimate the number of pregnant women during a period of time and then calculating the incidence of HDP based only on pregnant women, the results showed the lowest incidence in the group aged 25–29 years, similar to the results of previous studies. In general, HDP is more likely to occur at the extremes of reproductive age. Women of advanced maternal age are expected to have an increased rate of HDP because of risk factors such as obesity and diabetes [
21] and are more likely to develop atherosclerosis, which affects the small arteries, leading to hypertension [
17,
22]. Furthermore, teenage pregnancy is largely associated with adverse pregnancy outcomes such as preterm delivery, preeclampsia and low birth weight [
23]. These outcomes might be related to poverty, inadequate nutrition, poor health before pregnancy, marital status, or a low education level, which lead to limited healthcare knowledge among teenagers [
24].
In the GBD database, 87 risk factors were included, as they might cause 369 diseases or injuries globally, including environmental and occupational risks, such as air pollution; behavioral risks, such as iron deficiency; and metabolic risks, such as a high body mass index. In our study, only iron deficiency from the behavioral risk category was included as a risk factor for HDP in the population, while information on other risk factors was limited. However, previous studies have shown correlations between these “missing” factors and HDP progression. As a metabolic factor, women’s blood lipid levels change significantly in early pregnancy. Researchers have found that approximately 20–40 % of patients with preeclampsia have foam cell deposits in the subcutaneous fat and intraarterial cellulose and platelet aggregation [
25]. Data from a population study show significantly higher fasting triglyceride, total cholesterol and low-density lipoprotein-c levels in the HDP group than those in the healthy control group, and early detection of these parameters may help to better manage HDP [
26]. In addition, ambient air pollution, an important environmental risk factor, is a complex mixture composed of gases, aerosols, particulate matter (such as PM
10 and PM
2.5). The GBD results show that in 2019, only atmospheric PM
2.5 pollution directly or indirectly caused 6.67 million deaths and 213.28 million DALYs. Recently, some studies have discussed the possible association between air pollution and HDP [
27,
28]. A study recruited 22,041 pregnant women and found that exposure to high levels of air pollution in the early stage of pregnancy and throughout pregnancy were associated with HDP [particulate matter (PM
2.5): odds ratio (OR) = 1.33, 95 % CI: 1.18–1.49, NO
2: OR = 1.21, 95 % CI: 1.09–1.35, SO
2: OR = 1.13, 95 % CI: 1.01–1.25, CO: OR = 1.12, 95 % CI: 1.03–1.22] [
29]. Studies by Mobasher et al. suggested that only PM
2.5 exposure in early pregnancy (OR = 9.10, 95 % CI: 3.33–24.6) and CO exposure in the early and middle stages of pregnancy (early pregnancy: OR = 4.96, 95 % CI: 1.85–13.31, second trimester: OR = 2.05, 95 % CI: 1.22–3.46) increase the risk of HDP [
30]. Although indicators related to lipid metabolism and air pollution are included in the GBD database, relevant data were not available for the HDP analysis. Thus, we were only able to analyze behavior-related risk factors in this study, which was a limitation, and further investigation is also needed.
Our study found a decreasing trend in HDP due to iron deficiency from 1990 to 2019, which may be related to an increasing number of obstetricians prescribing iron supplements during pregnancy. However, some controversy still exists regarding the relationship between iron supplementation during pregnancy and the occurrence of HDP. Maintaining optimal iron levels is a delicate balance, with high levels associated with toxicity. One study found that pregnant women who subsequently developed HDP had lower serum iron levels in the first trimester than those who did not develop HDP. However, other studies showed different trends [
31]. Another study indicated higher serum iron levels measured at 20 weeks of gestation in women with preeclampsia but not gestational hypertension than in women with normotensive pregnancies [
32]. Differences in these findings are potentially explained by the use of different methodologies and gestational times of serum sample collection [
31]. Thus, adequate iron intake may be a concern in pregnancy [
33].
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