Comparison of Uric Acid Levels in Normotensive Pregnant Women and Women with Pregnancy Induced Hypertension

Introduction: Pregnancy induced hypertension and its complications are major causes of fetal and maternal morbidity and mortality. An association has been observed between pregnancy induced hypertension and serum uric acid levels. However assessment of 24-hour urinary uric acid excretion could glean further beneficial information. Since pregnancy induced hypertension leads to pre-eclampsia, determination of serum and urinary uric acid levels can be helpful in the management of this condition and its possible complications can be prevented. Aims & Objectives: The purpose of this study was to compare the uric acid levels in serum and 24-hour urinary samples during normal pregnancy and pregnancy induced hypertension. Place and duration of study: This study was conducted in the Department of Gynecology and Obstetrics, Shaikh Zayed hospital, Lahore in 2009. Material & Methods: This study included a total of fifty subjects, which were selected amongst the pregnant women attending the Outpatient Department of Gynecology and Obstetrics, Shaikh Zayed Hospital, Lahore. They were classified as group ‘A’ and group ‘B’ on the basis of recorded blood pressure, with each group comprising 25 pregnant women. Group A had normotensive and Group B had pregnancy induced hypertensive women. Blood and urine samples of all the 50 women were collected at 20 weeks, 24 weeks, 28 weeks, and 32 weeks of gestation and at term. Serum uric acid levels and 24-hour urinary uric acid samples were measured by clinical chemistry Autoanalyzer Dimension AR and recorded. Uric Acid Clearance was also calculated at mentioned weeks of gestation for comparison of the two groups. Results: The women in group ’A’ had normal serum uric acid levels and normal 24-hour urinary uric acid excretion. Whereas the women in group ’B’ had significantly raised serum uric acid values and decreased urinary uric acid excretion in a 24-hour urine sample during all gestational weeks. Conclusion: Women with pregnancy induced hypertension during all gestational weeks exhibited a positive correlation between blood pressure and serum uric acid levels, while a negative correlation was observation with 24-hour urinary uric acid excretion.


INTRODUCTION
As an established fact that, the pregnancy induced hypertension and its complications are major causes of fetal and maternal morbidity and mortality. An association has been observed between pregnancy induced hypertension and raised serum uric acid levels during gestation. Pregnancy induced hypertension may progress to pre-eclampsia, eclampsia and its complications. Pregnancy Induced Hypertension has been defined by the American College of obstetrics and Gynaecology as "Systolic blood pressure more than 140 mm of Hg and diastolic blood pressure more than 90 mm of Hg diagnosed after 20 weeks of uneventful gestation". 1 Based on strong evidence, pre-eclampsia and eclampsia can be included in the top prime instigators of maternal deaths all over the world. 2 In Pakistan, the statistics of maternal mortality due to eclampsia rise to 34% for women undergoing in patient management in a tertiary care hospital. 3 Hyperuricemia is reported as a key biochemical feature of PIH. 4 Rise in serum uric acid levels in PIH can be reliable indicator of pre-eclampsia and its perinatal complications. 5 Previously, it was thought that hyperuricemia during pregnancy is caused by its decreased renal clearance, but now it has been shown that trophoblast breakdown, cytokine release and cellular ischemia also contribute the production of uric acid. Hyperuricemia can promote endothelial dysfunctionn, cellular damage, inflammation and oxidation which might aggravate PIH. 6 Serum uric acid levels are not entirely dependable to assess fetal and maternal complications and the outcome can always be influenced due to the use of different therapeutic interventions. 7 The present study aimed to compare the uric acid levels in serum and its 24hr urinay excretion during normal pregnancy and PIH in our local setting.

MATERIAL AND METHODS
This study included a total of fifty subjects which were selected amongst the pregnant women attending the outpatient Department of Gynecology and Obstetrics, Shaikh Zayed Hospital, Lahore. They were grouped as group 'A' and group 'B' containing 25 pregnant women each on the basis of their blood pressure. Normotensive Patients were assigned to group 'A' and those with pregnancy induced hypertension to group 'B'. Blood and urine samples of all the 50 women were collected at 20 weeks, 24 weeks, 28 weeks, 32 weeks gestation and at term. Serum uric acid levels and 24-hour urinary uric acid samples were measured by clinical chemistry Autoanalyzer Dimension AR and recorded. Uric Acid Clearance was also calculated from 24 hrs urinary uric acid excretion at mentioned weeks of gestation for comparison of the two groups. Inclusion Criteria: Twenty-five pregnant women with normal blood pressure and 25 women with pregnancy induced hypertension were included in this study. Exclusion Criteria: Pregnant women with known hypertension due to cause other than pregnancy, gout, diabetes, renal, liver and cardiac diseases were excluded from this study.

Statistical analysis:
Data was analyzed on SPSS-21. Mean and standard deviation (SD) were computed and t-test and ANOVA were employed to find out significant difference and correlations between the variables, respectively. The p-value less than 0.05 was taken significant.

RESULTS
The women in group 'A' had normal values of serum uric acid and normal 24-hours urinary uric acid excretion throughout gestational weeks. The women in group 'B' developed a gradual rise in blood pressure with increasing gestational age (Table-1), with significantly raised serum uric acid levels and decreased 24 hours urinary uric acid clearance at 20 weeks, 24 weeks, 28 weeks, 32 weeks and at term (Table-2, Fig-1

DISCUSSION
Pregnancy may lead to raised blood pressure levels in previously normotensive women which is known as pregnancy induced hypertension. 8 Pregnancy induced hypertension remains a major health problem with adverse maternal and fetal out comes. It is responsible for 14% of maternal deaths in the world. 9 Women with raised uric acid values in their serum had twice the risk of developing severe hypertension, eclampsia and even perinatal mortality. 7 Serum uric acid level may be a marker of progression to pre-eclampsia among women with pregnancy induced hypertension. 10 In a study, high sensitivity and specificity of serum uric acid levels in assessing the risk of developing PIH have been reported. 11 Increased serum uric acid level in pregnancy induced hypertension cause aggravation of inflammation, endothelial dysfunction and oxidative stress which may explain why uric acid acts as an indicator for the progression of preeclamsia. 12 In another study, it was observed that, the reduction in 24 hours urinary uric acid excretion in women with pregnancy induced hypertension is a result of decreased filtration rate through the glomerulus and increased reabsorption of uric acid in proximal tubules of the kidneys. 13 During a similar study significant rise in serum uric acid levels in women with pregnancy induced hypertension was reported and it was concluded that, the monitoring of serum uric acid level is an easy and economical way to assess the severity of hypertension during pregnancy. Serum uric acid can still serve as an indicator for risk assessment in women with hypertension in pregnancy. 14 Results of our study are comparable with the other similar reported studies conducted under different circumstances in different parts of the world.

CONCLUSION
In this study, women with pregnancy induced hypertension during all gestational weeks exhibited a positive correlation between their blood pressure and serum uric acid levels which was raised progressively and a negative correlation with 24hr urinary uric acid excretion. Therefore, serum and urinary uric acid can both serve to foretell the chances of developing severe complications such as pre-eclampsia and eclampsia in women with pregnancy induced hypertension and allow for timely medical interventions to prevent complications.