Journal of Preventive Medicine

Introduction
Hypertensive disorders of pregnancy are among the primary causes of maternal mortality around the world. Preeclampsia is one of these disorders which affects 2-8% of pregnancies. To date, different methods have been used for the prevention of preeclampsia or reduction of its severity; however, none of these methods have been completely effective in reducing the rate of preeclampsia. Termination of pregnancy is the definitive treatment for preeclampsia; however, its complications such as high blood pressure and seizure can occur few days after delivery. Furthermore, in 0.3-27.5% of cases, the new preeclampsia develops in the postpartum period. Postpartum hypertension is the main reason for the majority of hospital re-admissions. It is caused by changes in fluid status and sodium balance in the context of preeclampsia. Postpartum hypertension is a cause of increased maternal mortality. Therefore, continued treatment after giving birth is necessary, especially in the first few days. Given the cause of postpartum hypertension (remobilization of the fluid to the intravascular space), it seems that the administration of diuretics can help by increasing fluid excretion. Despite the evidence on the efficacy of loop diuretics for the prevention of persistent postpartum hypertension, these medications have not yet been approved for women with preeclampsia. This study aimed to evaluate the efficacy of furosemide in controlling hypertension after Cesarean section (CS) in women with mild preeclampsia. 

Methods
This double-blind placebo-controlled randomized clinical trial was conducted on 120 women with mild preeclampsia after CS in Khalije Fars Hospital, Bandar Abbas, south of Iran, in 2017. The inclusion criteria were the definitive diagnosis of preeclampsia, delivery by CS, age 18-50 years, and systolic blood pressure of at least 140-159 mm Hg and diastolic blood pressure of at least 90-109 mm Hg, assessed every 4 hours during 24 hours after delivery. The exclusion criteria were a history of chronic hypertension, kidney diseases, liver diseases, diabetes mellitus, cardiovascular diseases, smoking, sensitivity to furosemide, and multiple pregnancy. The participants were randomly allocated to two groups using the sealed envelopes. One group received oral furosemide (20 mg daily for five days) and the other received placebo (daily for five days). The patients and researchers were unaware of the administered drug/placebo. Systolic and diastolic blood pressure, mean arterial pressure, and heart rate were measured in all patients on days 0 (before treatment), 1, 3, 5, and 7 after delivery. After seven days, if a patient had systolic blood pressure lower than 140 mm Hg and diastolic blood pressure lower than 90 mm Hg (both conditions simultaneously), it was regarded as having controlled blood pressure. Data were analyzed in SPSS software , version 19 using independent t-test and chi-square test. 

Results 
In this study, 120 women with mild preeclampsia participated, 60 in the furosemide group and 60 in the placebo group. There was no significant difference in terms of age (P=0.283) and weight (P=0.749) between the two groups. At baseline, there was no significant difference between the two groups regarding systolic blood pressure (P=0.396) and diastolic blood pressure (P=0.336), mean arterial pressure (P=0.536), and heart rate (P=0.399). However, systolic blood pressure was significantly lower in the furosemide group on days 1 (P<0.001), 3 (P=0.001), 5 (P=0.006), and 7 (P=0.006) compared to the placebo group. Moreover, diastolic blood pressure was significantly lower in the furosemide group on day 1 (P=0.001) compared to the placebo group. Although diastolic blood pressure was also lower in the furosemide groups at other time points, the difference between the two groups was not statistically significant. In addition, mean arterial pressure was significantly lower only in the furosemide group on days 1 (P<0.001) and 3 (P=0.021) compared to the placebo group; there was no significant difference at other time points. On the other hand, heart rate was not significantly different between the two groups at any time point. At the end of the treatment, blood pressure was controlled in 42(70%) patients in the furosemide group and 30(50%) patients in the placebo group, and this difference was significant (P=0.025).  

Conclusion
In this study, we evaluated the effect of oral furosemide on controlling high blood pressure after CS in women with mild preeclampsia and the results showed that 20 mg oral furosemide taken daily for five days after CS can significantly reduce systolic blood pressure on the 1st, 3rd, 5th, and 7th days after delivery compared to placebo. On the other hand, the percentage of women who had controlled blood pressure after treatment was significantly higher in the furosemide group. Therefore, the administration of oral furosemide is recommended for women with mild preeclampsia after CS to prevent hypertension.

Ethical Considerations
Compliance with ethical guidelines
The study was approved by the Ethics Committee of Hormozgan University of Medical Sciences (Code: IR.HUMS.REC.1396.017) and it complies with the statements of the Declaration of Helsinki. Also, it was registered by the Iranian Registry of Clinical Trials (IRCT) (Code:  IRCT20181218042033N3).

Funding
This article has been extracted from dissertartion of Narges Ghasemi’s for the degree of specialty in obstetrics and gynecology, approved by the Department of Obstetrics and Gynecology, School of Medicine, Hormozgan University of Medical Sciences, and was also was financially supported by  Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Authors' contributions
Conceptualization: Nazanin Abdi; Supervision: Saeed Hashemi; Formal analysis: Narges Ghasemi, Navid Abdi, and Ghazal Zoghi; Investigation and project administration: Narges Ghasemi; Data curation: Narges Ghasemi, and Navid Abdi; Writing the original draft: Nazanin Abdi, and Saeed Hashemi; Review and editing: Nazanin Abdi, and Ghazal Zoghi.

Conflicts of interest
The authors declared no conflicts of interest.

Acknowledgements
Collaboration of Clinical Research and Development Unit of Khalije Fars Hospital, Bandar Abbas, Iran, is appreciated and thanked.

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