Introduction

Hypertensive disorders in pregnancy are a major cause of maternal and fetal mortality, which complicate about 8% of all pregnancies (1). Preeclampsia is a specific hypertensive disorder of pregnancy that presents after 20 weeks of pregnancy and is reported in 2-7% of pregnancies. The prevalence of preeclampsia varies in different parts of Iran (2). Different studies performed on the prevalence of the disorder in the country, reported the prevalence rates of 1-8% for this disorder (3).

Despite extensive studies on this disease, its etiology is still unknown; accordingly, it was named as the disease of theories in 1916 (4). Many risk factors such as lifestyle (eating habits, sleeping, resting, physical activity, weight control, and smoking), psychological aspects, high hemoglobin level, and sleep disorders were considered for this disease (5-8).

Stress during pregnancy may indirectly or directly lead to increased complications of pregnancy. Levels of tumor necrosis factor-alpha and interleukin-6 pro-inflammatory cytokines are higher in women experiencing stress during pregnancy. On the other hand, the level of paired interleukin-10 (IL-10), which plays an important role in normal pregnancy, diminished in women with preeclampsia. Also, increased levels of corticotropin and increased activity in the sympathetic nervous system (SNS), which are the changes caused by stress, are observed in women with preeclampsia (1, 9).

Psychological aspects lead to overactivation of SNS due to the stimulation of autonomic nervous system that is a risk factor for preeclampsia (10). Previous studies showed that symptoms of anxiety or depression are associated with adverse pregnancy outcomes, such as preterm birth, birth weight less than 2500 gr, and small head circumference (11). However, there are few studies examining the association between psychological factors and preeclampsia. Some studies have shown a positive relationship between maternal psychological factors and preeclampsia (10).

According to the study of Kurki et al. (2000), stress and depression increased the risk of developing this disease 3.2 and 2.5-fold, respectively. Depression and anxiety during pregnancy due to the changes in the secretion of vasoactive hormones or other neuroendocrine transmitters, can lead to an enhanced risk of gestational hypertension (8).

The study of Qiu et al. (2007) demonstrated the relationship of depression and the symptoms of depression with an increased risk of preeclampsia (12). However, the study of Vollebregt et al. (2008) found no association between work stress, anxiety, depression, or anxiety related to pregnancy during the early stages and gestational hypertension or preeclampsia during pregnancy (1). According to the results of Kurki (2000), Vienna (2011), Qiu (2008), and Sigma (2001), pre-eclampsia is associated with anxiety, whereas the studies of Vollebregt (2000) and Anderson (2004) showed no relationship between anxiety and preeclampsia (1,8, 12-15).

A major problem midwives commonly witness is anxiety in pregnant women. Pregnancy is a stressful situation for most women and the reactions of women are different in this regard (2). There are conflicting results regarding the link between psychological aspects and hypertension, and a small number of studies have evaluated the relationship between psychological aspects and preeclampsia in Iran. Accordingly, we decided to examine the relationship between anxiety and preeclampsia. In so doing, we can prevent or lower the incidence of pree-clampsia and promote the chance of giving birth to a healthy neonate.

 Materials and Methods

This case-control study, after approval of the Research Ethics Committee of Mashhad University of Medical Sciences, was performed on 300 pregnant women (150 women with preeclampsia and 150 women without preeclampsia) who were referred to 12 health centers and three university hospitals of Mashhad in 2014. The sample size (based on a pilot study) with confidence coefficient of 95% and using the formula of ratio analysis with power of 80 was calculated as 133 cases that was increased to 150 women in each group.

The inclusion criteria included gestational age of 28 to 40 weeks (based on the first trimester ultrasound or the first day of the last menstrual period), maternal aged 35, singleton pregnancy, no hearing, speech, or mental problems, no diseases, having a body mass index of ≤29, and lack of stressful events during the last six months. The exclusion criteria comprised of withdrawal from participation in the study and use of antihypertensive drugs in the control group. Data collection tools included the demographic characteristics form, clinical and laboratory signs of preeclampsia, and Depression, Anxiety, and Stress Scale (DASS 21).

Prior to performing the study, the researcher introduced herself, explained the objectives and procedure of the study, obtained informed consent, and completed the information through an interview. The content validity of the demographic characteristics form and clinical and laboratory signs of preeclampsia was confirmed. The validity of the depression, anxiety, and stress scales of Doss was confirmed by Mollahadi in Iranian population (16), and its reliability was established in this study with Cronbach’s alpha coefficient of 0.86.

Inventory of depression, anxiety, and stress consisted of 21 items that were categorized into depression (n=7 items), anxiety (n=7 items), and stress (n=7 items). The questionnaire is rated using a 4-point Likert scale ranging from not at all to very high (score 0 to 3). The minimum and maximum possible scores range are 0 to 21, respectively. Since we used the short version of the questionnaire (the long form has 42 items), the scores were multiplied by 2 at the end. The cutoff point used for the presence of symptoms was depression ≥10, stress ≥15, and anxiety ≥8; the scores of 10-13, 8-9, and 15-18 were indicative of mild depression, anxiety, and stress, respectively. The scores of > 12, 20, and 34 demonstrated very severe depression, anxiety, and stress, respectively (10).The questionnaire was completed during prenatal visits.

In the control group, at first, among the areas with numbers of 1, 2, and 3 of Mashhad, 12 health centers were randomly selected. Once the control group was determined, the patients referred to the prenatal care were considered to be in proportion to the population of the centers. Furthermore, all the women without preeclampsia, with gestational age of 28 to 40 weeks, who met the inclusion criteria were selected by convenience sampling method.

In the case group, the pregnant women with gestational age of 28 to 40 weeks who met inclusion criteria and were monitored by the health centers during pregnancy or were hospitalized in the maternity wards of Imam Reza (AS), Ghaem, or Hashemi Nejad hospitals who had preeclampsia based on clinical and laboratory signs confirmed by physicians were selected by convenience sampling method. Preeclampsia was diagnosed acc-ording to systolic blood pressure of ≥ 140 mmHg or diastolic blood pressure of ≥ 90 mmHg, accompanied by urinary protein excretion of 300 mg/24 h or ≥+1 on a urine test strip, which was determined by observation of the criterion and blood pressure readings. These measurements were obtained by the researcher and approved by a gynecologist.

Blood pressure was measured by the researcher, taken from the right hand in a sitting position. If necessary, a urine sample was requested to assess urine protein. The women with no signs of preeclampsia, who were considered as the control group, were observed up to 24 h after delivery to ensure no incidence of preeclampsia and other problems. Those patients diagnosed with preeclampsia were removed from the control group and were entered into the case group. In case of pregnancy-induced hypertension without proteinuria, the patient was excluded from the study.

During the study, we excluded two patients due to preeclampsia, one due to gestational diabetes, and one due to hyperthyroidism. It should be noted that the control group received the questionnaire when they were waiting for prenatal care and sometimes after receiving care. Regarding the case group, they received the questionnaire when the subjects were admitted to the maternity ward, but before delivery. After delivery, the questionnaires were given to the patients about a day after delivery in the absence of patient’s companion.

The data was analyzed using descriptive and inferential statistical methods. Mann-Whitney U test was used to compare the quantitative variables between the two groups. Chi-square test was run to compare the qualitative variables between the two groups. Moreover, independent samples t-test was performed to compare quantitative variables with normal distribution, using SPSS version 16. P-value less than 0.05 was considered statistically significant.

 Results

The two groups were not significantly different in terms of maternal age (P=0.310), educational level (P=0.083), job (P=0.827). Therefore, the mean age of the mothers was 28.8±5.4 years in the case group and 27.5±4.9 years in the control group. In addition, 36 (24%) subjects in the case group had

elementary education and 52 (34.7%) in the control group had high school diploma. Furthermore, 141 (94%) patients in the case group and 164 (96%) in the control group were housewives. The two groups were also matched in terms of parity (P=0.118), gestational age (P=0.250), and husband's employment status (P=0.238; Table 1).

Chi-square test results showed that the two groups had significant difference in terms of anxiety (P<0.001; Table 2).

The mean score of anxiety in patients with preeclampsia (case group) was 10.0 ± 6.4, and in non-preeclamptic women (control group) it was 8.1 ± 5.7 (p=0.006).

Logistic regression was used to determine the association between history of abortion, body mass index, hemoglobin in the second trimester and hemoglobin in the second trimester with preeclampsia. The model results showed the body mass index, hemoglobin in the second trimester and anxiety had significant association with preeclampsia. It can be said that for every one-unit increase in anxiety, the risk of preeclampsia increases as 2.9-fold (Table 3).

 Discussion