Effect of Magnesium Sulfate on Doppler Parameters of Fetal Umbilical and Middle Cerebral Arteries in Women with Severe Preeclampsia

INTRODUCTION

Preeclampsia is defined as increase in systolic blood pressure ≥140 mmHg or diastolic ≥90 mmHg and proteinuria ≥300 mg protein/24 hours urine and starts after 20 weeks of pregnancy. Eclampsia is the condition in which generalized seizure occur in the absence of other neurologic defects.[1]

Preeclampsia and eclampsia are among the common causes of death and disability in pregnant women and are associated with increased vascular resistance and decreased uteroplacental perfusion.[2] It is characterized by vascular contraction, lesions in the placenta and umbilical arteries, high blood pressure, proteinuria, and seizure.

This disease can cause many fetal and maternal complications. Maternal complications include acute renal failure, liver damage, intracerebral hemorrhage, pulmonary edema, and death. Fetus complications are preterm birth or intrauterine growth restriction.[3–5]

Magnesium sulfate (MgSO₄) is used for the treatment of severe preeclampsia and can help prevent serious complications.[67] Effect of MgSO₄ on cerebral vessels are still controversial and it is unclear whether it reduces cerebrovascular vasospasm. Studies in this area are still ongoing.[8–11] The mechanism of action may include changes in vascular permeability and reduction of edema.[6] It seems to have no adverse effects on the fetus,[12] but in response to MgSO₄ injection, fetal brain perfusion may also alter.[13]

In pregnancy, usually umbilical artery is tested by Doppler ultrasound but some recent studies also test maternal and fetal middle cerebral arteries (MCA).[14–17] In one study, the reference value of resistive index (RI) and pulsatility index (PI) have been investigated in Iranian patients.[16] The ratio of middle cerebral artery/umbilical artery (C/U ratio) can be a good indicator of fetal prognosis and fetal well-being.[16–20]

Doppler ultrasound is a useful tool for studying pathophysiological mechanisms that can affect the fetal hemodynamic status.[192122] Assessing the changes in the arteries with Doppler ultrasound can show the adaptation of fetus to the situation.[1723] An increase in umbilical artery resistance shows as a decrease in perfusion. If the situation continues, RI in the middle cerebral artery will decrease.[24] Investigating the mechanism of action of MgSO₄ on the fetus is one of the important issues in this disease.[25] The purpose of this study is to evaluate the effect of MgSO₄ in severe preeclampsia on fetal middle cerebral artery and umbilical artery using Doppler parameters.

MATERIALS AND METHODS

This is a quasi-experimental study (before-after). This study was approved by the ethics committee of Kermanshah University of Medical Sciences. Patients who needed injections of MgSO₄ were included in the study. MgSO₄ injection was administered under the supervision of a gynecologist. Prior to the intervention, Doppler ultrasound was used to evaluate the fetal middle cerebral and umbilical arteries of the patients.

Patients with severe preeclampsia who attended Imam Reza hospital, Kermanshah Iran during the period 2011-2012 were included in the study. Inclusion criteria were: Age in the range of 20-35 years, first pregnancy, gestational age above 28 weeks, systolic blood pressure ≥140 mmHg, and diastolic pressure ≥90 mmHg with the proteinuria of at least 300 mg in 24 hour urine or having urinary protein level ≥ +2, and epigastric pain. Exclusion criteria were: Any type of systemic disease (e.g., diabetes, hypertension, and autoimmune disorders), history of taking opium, smoking, twin pregnancy, and history of taking specific drugs.

During the study period 21 patients were evaluated. The goal of the study and the method were described to all patients and written consent form was taken prior to the initiation of study.

After admission of the patient in a room that had cardiopulmonary resuscitation (CPR) facilities, a radiologist recorded the color Doppler ultrasound of fetal umbilical and MCA, using a Siemens Ultrasound device (Germany), model G40, with a deep probe of 3/5-5 MHz. The mean RI and PI of MCA from the proximal part of two MCA arteries (left and right) and the C/U ratio (middle cerebral artery RI/umbilical artery RI) were evaluated. Parameters related to the umbilical artery close to the navel were evaluated.

RI = Peak systolic velocity - end diastolic velocity/peak systolic velocity

PI = Peak systolic velocity - end diastolic velocity/mean velocity

After initial assessment, a gynecologist injected the primary and maintenance dose of MgSO₄. The primary dose had 14 g of MgSO₄ of which 4 g in the form of a 20% solution was injected intravenously for at least 4 min and then immediately 10 g of MgSO₄ in the form of 50% solution was injected muscularly. Twenty minutes after intravenous injection (4 g), Doppler ultrasound was again performed to measure blood flow in fetal MCA and umbilical arteries.

Data were analyzed using SPSS version 11.5 software (SPSS Inc., Chicago, IL, USA). Kolmogrov-Smirnov test was used to prove the normal distribution of variables and all variables had normal distribution. Then the before and after intervention values were compared by Paired t-test. A level of 0.05 was considered significant.

RESULTS

In the 21 patients studied, average RI-umbilical before and after the intervention were 0.72 ( ±0.1) and 0.62 (±0.09), respectively, which showed a statistically significant decrease (P < 0.001). The before and after PI-umbilical values were 1.35 ( ±0.47) and 1.28 ( ±0.49), respectively, which was not a significant change (P = 0.1). In addition, the average before and after RI-MCA were 0.71 (±0.16) and 0.71 (±0.11), respectively, and this particular index did not show any significant change (P = 0.96). But, a statistically significant decrease (P = 0.001) was observed in the average amount of before PI-MCA 1.63 (±0.84) and the after value 1.47 (±0.69). According to calculations, the before C/U ratio value was 1 (±0.26) and the after value was 1.17 ( ±0.29), which showed a statistically significant increase (P < 0.001) [Figure 1]. The power of the test to compare before and after PI-umbilical values was calculated as 61.6% and 33.3% for RI-MCA.

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Figure 1

Comparison of resistivity index (RI) and pulsatility index (PI) of umbilical and middle cerebral artery and C/U ratio before and after 20 min of administering magnesium sulfate (MgSO₄) injection.

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DISCUSSION

This study investigated the effect of administration of MgSO₄ in severe preeclampsia cases on fetal umbilical and MCA blood flow. Based on the results of this study, the injection of MgSO₄ could significantly decrease the RI-umbilical, PI-MCA, and increase C/U ratio.

Fetal distress caused by hypoxia is one of the effects of preeclampsia on the fetus. Probably, circulation disorder is the most important cause of hypoxia and distress.[26] Inadequate placental perfusion can cause fetal reduction of oxygen supply, and thus lead to fetal distress.[2127]

Several studies have shown the medical effects of MgSO₄ in treating patients with preeclampsia and eclampsia.[2829] Souza et al,[3031] assessed fetal MCA and umbilical artery Doppler parameters and measured these parameters 20 min after injection of MgSO₄. They showed that umbilical and MCA RI and PI values are significantly reduced. While in our study these parameters showed no significant change.

In addition, another study showed the reduction of PI in the fetal umbilical artery and MCA due to the injection of MgSO₄.[30] In Dasgupta's study, when compared with control group, the umbilical artery PI value decreased, but the fetal MCA-PI did not change significantly.[32] In another study, the MCA did not change.[33] The impaired perfusion in fetal MCA can be associated with hypoxia and fetal complications.[2434]

In our study, after injection of MgSO₄, C/U ratio had a significant increase, which shows that the fetal blood supply had improved. Various studies confirmed the efficacy of Doppler ultrasound examination for assessing the vascular status of the fetus and have introduced the C/U ratio as a parameter in assessing fetal blood supply.[35] The C/U ratio shows both inadequate fetal circulation and changes and adaptations in the artery.[17] Hence, this drug (MgSO₄) can cause vasodilatation in the fetal umbilical artery.[36] Some studies did not show the same result.[3031] The fetal MCA resistance increases in normal pregnancy slightly[21] and the increase is more substantial in preeclampsia and eclampsia. The administration of MgSO₄, therefore, can have beneficial effects on the fetus and can increase perfusion. C/U ratio is a good indicator for assessing the growth and prognosis of the fetus, while the fetal MCA alone does not have the same value.[3738]

This study also had certain limitations. One of the limitations of this study was the lack of a control group. However, due to the special status of patients with severe preeclampsia, there are inevitable limitations in the design of this study and similar studies. The small sample size was another limitation, which reduced the test power of PI-umbilical and RI-MCA to less than 80%. The lack of significant statistical differences in these two indicators might result from the small sample size of patients. Results of our study and studies of others indicate more extensive studies with larger patient numbers are required to be conducted and if possible a meta-analysis of the results of all existing studies to confirm conclusions about the effects of MgSO₄ on fetal blood flow is also essential.

CONCLUSIONS

Infusion of MgSO₄ significantly decreases the fetal RI-umbilical and PI-MCA and increases C/U ratio indices obtained with color Doppler ultrasound evaluations.