Risk factors and potential protective factors of pregnancy‐induced hypertension in China: A cross‐sectional study

Abstract

A cross‐sectional study was conducted to the reported factors and assesses possible protective factors for pregnancy‐induced hypertension (PIH) in China. The data of pregnant women who delivered between October 2016 and September 2017 were collected from a birth registry. The primary outcome was the occurrence of PIH. Secondary outcomes were delivery before 34 gestational weeks and other adverse obstetric outcomes of PIH. Among the 99 535 women enrolled, 5731 women (5.8%) developed PIH. BMI had a positive correlation with the primary and two secondary outcomes (adjusted OR = 2.05, 2.56, 1.87, respectively, for overweight; adjusted OR = 4.44, 3.90, and 2.63, respectively, for obesity). Otherwise, calcium supplementation during pregnancy was a potential protective factor for those outcomes (adjusted OR = 0.87, 0.14, and 0.44, respectively). These results provide a basis for PIH prevention strategy in the Chinese public health sector. Calcium supplementation and lowering the BMI might have the potential benefit on reducing the prevalence of PIH in selected women.

1. INTRODUCTION

Pregnancy‐induced hypertension (PIH) is a common pregnancy‐related complication and one of the main causes of perinatal morbidity and mortality. Worldwide, the prevalence of PIH has been reported to range from 4.6% to 13.1%,1, 2, 3, 4, 5 contributing to 9.2% of neonatal deaths. Several studies have highlighted the risk factors for PIH, including but not limited to primiparity, advanced maternal age, multiple pregnancy, assisted reproduction technique (ART), obesity, gestational diabetes mellitus, thrombocytopenia, previous or family history of PIH, and complications associated with placental dysfunction such as small for gestation age, placental abruption, or stillbirth.6, 7 Preexisting medical problems such as chronic hypertension and diabetes mellitus also significantly increased the risk of PIH.6, 7, 8

The priori risk in pregnant women, which is based on individual relevant factors, is race‐specific and should be adjusted accordingly.9, 10 However, the available data are limited on Asian race. Given differences in genetic variant, diet habits, ethnicity, and geography, it is important to get relevant information among Chinese women to make up the deficiency of current researches on Asian race. We suppose that this study will validate some known factors and protective factors which are either specific or important for Chinese population.

2. METHODS

The protocol was approved by the Ethics Committee of PUMCH: JS‐1151. Because of a retrospective register study, the need for informed consent was waived. Using the National Birth Registry of China, we conducted a multicenter retrospective cohort study in order to evaluate multiple risk factors for PIH in the Chinese population. The researchers had selected 14 representative hospitals in 10 provinces from 4 major economic zones in China (including 2 secondary and 12 tertiary hospitals, 7 general hospitals, and 7 women and children's hospitals). Specially assigned persons at each hospital were responsible for collecting and reporting information of pregnant women who delivered between October 1, 2016 and September 30, 2017, through an Internet‐based system using a birth registration platform. All deliveries in the hospitals after 20 weeks of gestation were included, and complete medical information for each birth, including maternal age, parity, prepregnancy body mass index (BMI), maternal and fetal outcomes, gynecological and obstetric history, major medical history, major family history, and calcium supplementation during pregnancy, was recorded. The advanced age is defined as 35 years or older at delivery. BMI before pregnancy was recorded and classified according to the Chinese reference standards. A BMI between 18.5 and 23.9 kg/m² was considered as normal, between 24 and 27.9 kg/m² was considered overweight, and equal to or >28 kg/m² was considered obese.11 During pregnancy, calcium supplementation is usually 600 mg per day. Data of the eligible cases were entered into the data collection system and were ultimately exported from the central database system.

The primary outcome of this study was PIH, including gestational hypertension, preeclampsia or eclampsia with/without chronic hypertension. Chronic hypertension without superimposed preeclampsia was not included. All the conditions were defined according to guidelines from the American College of Obstetricians and Gynecologists.12 Secondary outcomes included delivery before 34 weeks of gestation and other adverse pregnancy outcomes in patients with PIH. Premature delivery (before 34 weeks of gestation) was strongly associated with adverse outcomes and was analyzed separately.13 Other adverse outcomes were defined as any of the following: placental abruption, eclampsia or HELLP syndrome, maternal death, severe neonatal asphyxia (neonatal Apgar score ≤3 at 5 minutes) or perinatal death, and small for gestational age.

The statistical analyses were performed using Statistical Package for Social Sciences (SPSS Inc). Firstly, we confirmed the number of each variable and excluded variables with missing data ≥10%. For each enrolled variable, we calculated the prevalence of PIH. Secondly, we compared all enrolled variables of two groups by using binary analysis. The independent t test was used for continuous variables. The chi‐squared test (χ ²) was used for categorical variables. The logistic regression analysis was used for multivariable analysis and 95% confidence intervals (CIs). The step‐backward logistic regression was based on P value. Between PIH group and non‐PIH group, the variables with statistically significant difference in the binary analysis were entered into the original model for multivariable analysis. The final model was obtained by a step‐backward logistic regression analysis. The results of multivariate analysis were the independent relevant factors for PIH. All P values were two‐sided, and P values < 0.05 were considered statistically significant.

3. RESULTS

3.1. The basic characteristics of participants

A total of 99 535 deliveries were enrolled in the study. Of the 5731 women (5.8%) who developed PIH, 1515 (1.5%) had gestational hypertension, and 4216 (4.3%) had preeclampsia/eclampsia, including 457 (0.5%) chronic hypertension superimposed with preeclampsia, 73 (0.07%) eclampsia, and 82 (0.08%) HELLP syndrome. The baseline demographic characteristics and available clinical characteristics are shown in Table 1. The average period of gestation in women without PIH was 38.9 weeks (standard deviation SD = 2.0), whereas it was 37.0 weeks (SD = 3.2) in women with PIH (P < 0.001).

Table 1.

The baseline demographic and clinical characteristics (n = 99535)

Demographic characteristics and clinical characteristics	Valuea
Continuous variable
Maternal age (y)	30.7 (16‐60)
Gravidity	2.2 (1‐14)
Parity	1.3 (0‐7)
Delivery gestational week (wk)	38.8 (20.0‐41.86)
Categorical variables
Advanced maternal age (≥35)	20615/99535 (20.7%)
Primiparity	8147/99535 (8.2%)
BMIb 24‐28 kg/m2	9917/69302 (14.3%)
BMI ≥28 kg/m2	1964/69302 (2.8%)
Cesarean section	45534/99268 (45.9%)
Multiple pregnancy	3140/98948 (3.2%)
Assisted reproduction techniques (ART)	3421/96869 (3.5%)
Pregnancy‐induced hypertension (PIH)	5731/99535 (5.8%)
Placental abruption	843/99535 (0.8%)
Delivery before 34 gestational weeks	3862/99535 (3.9%)
Small for gestational age	564/99535 (0.6%)
Neonatal asphyxiac	1475/99535 (1.5%)
Stillbirth and/or neonatal death	640/99535 (0.6%)
Chronic hypertensiond	637/99534 (0.6%)
Diabetes mellituse	522/86849 (0.6%)
Chronic renal diseasef	331/99534 (0.3%)
Heart diseaseg	878/99535 (0.9%)
Viral hepatitis	2672/99535 (2.7%)

^aThe value is expressed as the mean X (range) or the number n (%).

^bBMI, body mass index. In the study, the grading criteria are based on the recommendation in China Diabetes Prevention Guidelines and the Chinese Adult Standards proposed by the International Life Sciences Institute China Obesity Working Group in 2004:18.5‐23.9 is normal value, 24.0‐27.9 is overweight, and >28 is obese.

^cNeonatal asphyxia is defined as Apgar score ≤3 at 5 min.

^dChronic hypertension was defined as systolic/diastolic BP ≥140 or diastolic ≥90 mm Hg prior pregnancy or before 20 wk of gestation according to the 2008 Scientific Statement.

^eDiabetes mellitus was defined as glycated hemoglobin (A1C) ≥6.5%, fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L), random elevated glucose ≥200 mg/dL (11.1 mmol/L), or 2‐hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an 75 g oral glucose tolerance test (OGTT) according to the 2010 American Diabetes Association (ADA) guideline.

^fChronic renal disease mainly includes chronic glomerulonephritis, chronic pyelonephritis, diabetic nephropathy, hypertensive nephropathy, and autoimmune nephropathy.

^gHeart disease includes congenital heart disease, rheumatic heart disease, cardiomyopathy, hypertensive heart disease, hyperthyroid heart disease, anentic heart disease, arrhythmia, myocarditis, infective endocarditis, cardiomyopathy, valvular disease, and coronary heart disease.

3.2. The risk factors for pregnancy‐induced hypertension

The results of the details of multivariate logistic regression analysis of risk factors for PIH are shown in Table 2. After multivariable analysis, chronic hypertension (adjusted OR = 31.91, 95% confidence interval [CI]: 25.70‐39.63) and PIH in the previous pregnancy (adjusted OR = 31.91, 95% CI: 17.48‐32.36) were the two strongest risk factors for PIH. Other independent risk factors were chronic renal disease (adjusted OR = 2.54), heart disease (adjusted OR = 2.05), BMI 24‐28 kg/m² (overweight, adjusted OR = 2.05), multiple pregnancy (adjusted OR = 2.01), and other moderate risk factors like thrombocytopenia, diabetes mellitus, weekly weight gain exceeding 0.5 kg during pregnancy, history of preterm birth or late abortion, gestational diabetes mellitus, ART, uterine fibroid, and advanced maternal age (adjusted OR < 2.0). Primiparity was not found to be independently associated with PIH (Table 2). Additionally, we found overweight (adjusted OR = 2.05, 95% CI: 1.73‐2.33) and obesity (adjusted OR = 2.05, 95% CI 3.91‐5.05) had a positive correlation of BMI with PIH. Calcium supplementation during pregnancy had a negative correlation with PIH which infer that calcium supplementation was a potential protective factor for PIH (adjusted OR = 0.87, 95% CI: 0.81‐0.94).

Table 2.

The adjusted risk factors for PIH

Characteristic	Adjusted OR	95% CI
Chronic hypertension	31.91	25.70‐39.63
Prior PIH	23.78	17.48‐32.36
BMI ≥28 kg/m2	4.44	3.91‐5.05
Chronic renal disease	2.54	1.73‐3.74
Heart disease	2.05	1.58‐2.67
BMI 24‐28 kg/m2	2.05	1.73‐2.33
Multiple pregnancies	2.01	1.73‐2.34
Weight gain exceeding 0.5 kg/wk	1.89	1.75‐2.04
Prior preterm birth/late abortion	1.74	1.43‐2.10
Thrombocytopenia	1.69	1.26‐2.26
Diabetes mellitus	1.68	1.16‐2.45
Gestational diabetes mellitus	1.48	1.36‐1.61
Uterine leiomyoma	1.45	1.25‐1.67
ART	1.40	1.21‐1.63
Advanced maternal age	1.25	1.16‐1.35
Calcium supplementation	0.87	0.81‐0.94

Abbreviations: ART, assisted reproduction techniques; BMI, body mass index; CI, confidence interval; OR, odds ratio; PIH, pregnancy‐induced hypertension.

3.3. The risk factors for pregnant women with PIH who delivered before 34 gestational weeks

For pregnant women with PIH who delivered before 34 gestational weeks, a multivariate analysis of selected risk factors was conducted in Table 3. Chronic hypertension (adjusted OR = 14.2, 95% CI: 10.67‐18.90) and PIH in previous pregnancies (adjusted OR = 12.28, 95% CI: 8.26‐18.28) remained the two strongest risk factors in pregnant women with PIH who delivered before 34 gestational weeks. Other moderate risk factors that corresponded to the primary outcomes were chronic renal diseases (adjusted OR = 4.15, 95% CI: 2.21‐7.81), multiple pregnancies (adjusted OR = 4.13, 95% CI: 3.00‐5.69), being overweight or obese (adjusted OR = 2.56, 95% CI: 2.10‐3.09, and 3.90, 95% CI: 2.94‐5.17, respectively), heart disease (adjusted OR = 2.66, 95% CI: 1.61‐4.40), advanced maternal age (adjusted OR = 1.64, 95% CI: 1.37‐1.96), and ART (adjusted OR = 1.60, 95% CI: 1.15‐2.23). History of placental abruption (adjusted OR = 4.34, 95% CI: 1.46‐12.94), stillbirth (adjusted OR = 2.47, 95% CI: 1.35‐4.50), and preterm birth/late abortion (adjusted OR = 2.03, 95% CI: 1.39‐2.97) were also independent risk factors. In addition, the presence of uterine fibroids was an independent risk factor for PIH (adjusted OR = 1.81, 95% CI: 1.25‐1.67), but it was not associated with the two secondary outcomes. We also found the potential protective effect of calcium supplementation (adjusted OR = 0.14, 95% CI: 0.09‐0.20).

Table 3.

The adjusted risk factors for PIH who delivered before 34 gestational weeks

Exposed factors	Adjusted OR	95% CI
Chronic hypertension	14.20	10.67‐18.90
Prior PIH	12.28	8.26‐18.28
Prior placental abruption	4.34	1.46‐12.94
BMI ≥28 kg/m2	3.90	2.94‐5.17
Chronic renal disease	4.15	2.21‐7.81
Multiple pregnancy	4.13	3.00‐5.69
Prior stillbirth or neonatal death	2.47	1.35‐4.50
Heart disease	2.66	1.61‐4.40
BMI 24‐28 kg/m2	2.56	2.10‐3.09
Thrombocytopenia	2.32	1.23‐4.37
Prior preterm birth/late abortion	2.03	1.39‐2.97
Maternal age ≥35	1.64	1.37‐1.96
ART	1.60	1.15‐2.23
Calcium supplementation	0.14	0.09‐0.20

Abbreviations: ART, assisted reproduction techniques; BMI, body mass index; CI, confidence interval; OR, odds ratio; PIH, pregnancy‐induced hypertension.

3.4. The risk factors for other adverse outcomes of PIH

The risk factors for other adverse outcomes of PIH were evaluated using multivariable analysis, and the data are summarized in Table 4. We found that the risk factors were similar for both secondary outcomes. The positive correlation of BMI was observed with other adverse outcomes of PIH, which were overweight (adjusted OR = 1.87, 95% CI: 1.50‐2.34) and obese (adjusted OR = 2.63, 95% CI: 1.85‐3.75). Calcium supplementation during pregnancy was a potential protective factor (adjusted OR = 0.44, 95% CI: 0.31‐0.62).

Table 4.

The adjusted risk factors for PIH with other adverse outcomes

Exposed factors	Adjusted OR	95% CI
Chronic hypertension	12.95	9.27‐18.10
Previous PIH	11.77	7.39‐18.73
Prior placental abruption	6.04	1.85‐19.76
Thrombocytopenia	4.13	2.38‐7.15
Renal disease	3.24	1.56‐6.73
Multiple pregnancy	3.09	2.19‐4.36
BMI ≥28 kg/m2	2.63	1.85‐3.75
Heart disease	2.28	1.27‐4.09
Prior preterm birth/late abortion	2.26	1.45‐3.51
BMI 24‐28 kg/m2	1.87	1.50‐2.34
Weight gain exceed 0.5 kg/wk	1.50	1.18‐1.89
Maternal age ≥35	1.28	1.03‐1.57
Calcium supplementation	0.44	0.31‐0.62

Abbreviations: ART, assisted reproduction techniques; BMI, body mass index; CI, confidence interval; OR, odds ratio; PIH, pregnancy‐induced hypertension.

4. DISCUSSION

The present study was a multicenter retrospective cross‐sectional study in China using a national birth registry to analyze the risk factors for PIH in Chinese women. The incidence of PIH in the current Chinese population is higher than that reported in 2011.6 This increase is partly attributable to the increased occurrence of certain relevant factors such as advanced maternal age, ART, and obesity.14 Most of the reported relevant factors for PIH were confirmed in our study, and these findings may help identify high‐risk women and provide them with proper medical care. Chronic hypertension and PIH in previous pregnancies were strong correlation with PIH. Moreover, in our study, the presence of uterine fibroids was an independent risk factor for PIH. This may be explained by the impaired invasiveness of trophoblast cells in some women with uterine fibroids,15 which was considered as the mechanism of PIH.

In our results, advanced maternal age (over 35 years of age) was observed to be positively associated with PIH (OR = 1.25). There was some supportive data from different countries, such as Australian, Latin American, and Caribbean.16, 17, 18 They all support the maternal age as a risk factor for PIH (OR range 1.67‐2.34). Since the change in the Chinese one‐child policy to the two‐child policy in 2013, the demographic characteristics of pregnant women have been greatly altered. The proportion of women with advanced maternal age was as high as 20.7% in our study, similar to a previous report with a proportion of 22%.19 Delayed childbearing age increases the occurrence of gestational hypertension, as well as other complications such as gestational diabetes mellitus, stillbirth, neonatal intracranial hemorrhage, and fetal malformations.20 This may pose a new challenge to obstetric providers in China.

The positive correlation between BMI and prevalence of PIH and related adverse pregnancy‐related outcomes were observed in our study. Compared with women with a normal BMI before pregnancy, the overweight and obese women demonstrated a 2.05‐ and 4.44‐fold higher prevalence of PIH. The consistent conclusion has also been drawn in Pakistani and White British population.21 The prevalence of PIH increased with prior pregnancy BMI increasing. A meta‐analysis of 29 studies has shown the positive association between prior pregnancy BMI and PIH from various countries.22 According to our result, about 17.1% of pregnant women were overweight or obese in China. It has been reported that the proportion of overweight or obese Chinese women has increased significantly in the last two decades, and this trend will continue to increase to high levels.23 Between 1993 and 2009, the overweight rates increased from 10.7% to 14.4%, and the obesity rates increased from 5.0% to 10.1% in the general Chinese population.23, 24 In 2014, the overweight and obesity rates in women aged 15‐54 years in southern China reached 23.0% (1045/4540) and 6.1% (277/4540), respectively.25 Obesity per se may cause many health problems, such as diabetes mellitus, cardiovascular disease, and metabolic syndrome.26 As observed in our study, overweight and obesity, diabetes mellitus, and heart diseases were independent risk factors for PIH. We recommend maintaining the prior pregnancy BMI in the healthy range to reduce the risk of the onset of PIH and adverse pregnancy outcomes of PIH.

Previously published studies demonstrated that serum calcium and magnesium levels are lower in women with PIH than in women with normal pregnancies.27 Women with a low calcium intake may be prone to developing hypertension, especially those who had suffered PIH previously.28 Hence, calcium supplementation during pregnancy may be a potential protective factor for PIH. In our study, calcium supplementation was associated with a significant reduction in PIH (OR = 0.87), especially in women with PIH who delivered before 34 weeks of gestation (OR = 0.14) or who have other adverse pregnancy‐related outcomes (OR = 0.44). Chinese population follows the diet with insufficiency calcium. An investigation in China demonstrated that more women lived in cities would take calcium supplementation than those lived in rural areas.29 However, this effect may be biased, as data on the serum calcium levels and detailed dosage or duration of calcium supplementation were insufficient. The role of calcium in preventing PIH is controversial, and further research is warranted on the effects of calcium supplementation on PIH; however, the Index to Social Sciences & Humanities Proceedings still advocates calcium supplementation during pregnancy.13

Primi‐gravidity has been reported as a relevant factor of PIH and preeclampsia in other countries.16, 30 The evidence among Indians showed an inconsistent result.31 In 2005, there was a single‐center investigation in China, which supported primi‐gravidity as a risk factor for PIH.32 The role of primi‐gravidity for PIH was controversial. In our study, primi‐gravidity was not independent risk factor for PIH. But this result should be interpreted with caution. With the two‐child policy replacing the one‐child policy recently in China, the demographic characteristics of pregnant women have been greatly altered. The proportion of women with advanced maternal age was as high as 20.7% in our study. In addition, multigravity women might have long pregnancy interval. These factors can increase their risk and mask the primi‐gravity as a risk factor for PIH. Thus, the change of demographic characteristic of pregnant women in China may explain the absent effect of primi‐gravidity on PIH incidence.

We found that chronic hypertension and previous history of PIH were significant risk factors for PIH in the Chinese population, which is comparable to findings of previous reports. Calcium supplementation and lowering the BMI might have the potential benefit on reducing the prevalence of PIH in selected women. The occurrence of risk factors such as advanced maternal age and high BMI has dramatically increased, and hence, more attention should be paid to these trends in order to reduce the risk of PIH in pregnancy. These results provide a basis for PIH prevention strategy in the Chinese public health sector. Well‐designed prospective clinical trials regarding the risks and protective factors for PIH are warranted in the future.

The advantages of our study are, it is a multicenter big data of pregnant women with PIH, and subgroup analysis was conducted by various pregnancy outcomes. In this study, we investigate 14 potential risk factors, 1 potential protective factor, and 3 maternal and neonatal adverse outcomes in Chinese population. However, several limitations exist. We could only analyze factors with complete information in this retrospective research; therefore, some known factors could not be evaluated, such as hereditary factors,6 genetic variants,33 socioeconomic status,34 education,32 seasonal variation (climate),3 due to missing data ≥10% or not recorded in our database. As few women continue smoking or drinking alcohol during pregnancy, the effect of smoking habit,16 and alcoholic habit,30 on PIH cannot be evaluated.

CONFLICT OF INTEREST

None.

Supporting information

 

Zhuang C, Gao J, Liu J, et al. Risk factors and potential protective factors of pregnancy‐induced hypertension in China: A cross‐sectional study. J Clin Hypertens. 2019;21:618–623. 10.1111/jch.13541