IJCRR - Vol 08 Issue 05, March
Date of Publication: 13-Mar-2016
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ACCURACY OF SERUM URIC ACID IN PREDICTING COMPLICATIONS OF PRE-ECLAMPSIA
Author: A. Ramana Priya, K. Jeyapriya, N. S. Kannan
Abstract:Introduction: Pre-eclampsia, is a pregnancy-specific syndrome that occurs after mid gestation comprising of gestational hypertension with significant proteinuria. If not treated properly will lead to maternal and foetal complications. Aims: To study the accuracy of serum uric acid in predicting complications of pre-eclampsia and its effect on pregnancy outcome. Methods: Sixty pregnant women at term gestation with diagnosis of pre-eclampsia were included in our study after informed consent. For all patients included in the study all routine investigations including serum uric acid were done and recorded. All the patients were followed up until delivery and all maternal and foetal events were recorded. All complications of pre-eclampsia both maternal and foetal were statistically analysed to prove the predictive value of serum uric acid levels. Results: 18.3% of mothers were between the age group 18-21 years, 26.7% were between 22-25 years, 28.3% were between 26-29 years, and 26.7% were above 30 years. 83.4% of 60 mothers were primi para, 8.3% were para 2, and 8.3% were para 3. The difference in the first minute APGAR in the high risk and no risk category was not statistically significant at p value of 0.1798. The difference in the 5th minute APGAR in the high risk and no risk category was statistically significant at p value of 0.001. 4 out of 42 women (9.52%) with serum uric acid ≥6mg/dl had maternal complications and 7 out of 18 women with serum uric acid < 6mg/dl had maternal complications (p value = 0.01) which is statistically significant. Considering less than 2.5 Kg as low birth weight, serum uric acid levels of more than 5.5 are associated with significant low birth weight (p value of 0.01) which is statistically significant. Conclusion: Our study with a sample size of 60 has proved that serum uric acid is statistically significant predictor (p value 0.01) of foetal complications of pre-eclampsia even though not of maternal complications (p value 0.42).
Keywords: Gestational hypertension, Eclampsia, HELLP syndrome, Maternal death, Intrauterine growth restriction, Foetal distress, Perinatal death
Pre-eclampsia, a pregnancy-specific syndrome that occurs after mid gestation, is defined by the de novo appearance of hypertension (systolic blood pressure of ≥140 mm Hg or diastolic blood pressure of ≥90 mm Hg), accompanied by new-onset proteinuria, defined as ≥300 mg per 24 hours1 . Previous definitions included oedema, but this sign is nonspecific and is observed in many normotensive pregnant women. Thus, oedema is no longer considered part of the diagnostic criteria for preeclampsia.
The incidence of preeclampsia is 2-10%, depending on the population studied and definitions of Pre-eclampsia2 . It can result in many maternal complications3,4 such as severe hypertension, eclampsia and HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low platelet count), or foetal complications5 such as growth restriction, foetal distress and even perinatal death. Early prediction of these complications might help to decide whether termination of pregnancy might be a better option than expectant monitoring.
AIMS AND OBJECTIVES:
Aims: To study the accuracy of serum uric acid in predicting complications of pre-eclampsia and its effect on pregnancy outcome. Objectives: 1. To estimate the serum uric acid levels in term gestation with pre-eclampsia. 2. To evaluate the relationship between serum uric acid and foetal outcome. 3. To know the association between the level of serum uric acid and severity of hypertension. 4. To correlate serum uric acid levels with maternal morbidity and mortality.
MATERIALS AND METHODS
A prospective study to estimate serum uric acid was carried out in 60 pregnant women at term gestation ( > 37 weeks of gestation) admitted in Raja Muthiah Medical College Hospital during the period October 2011 - September 2013 with diagnosis of pre-eclampsia (pregnancy induced hypertension and proteinuria with or without pathological oedema). These patients were included in the study after due informed consent. The criteria adopted to diagnose pregnancy induced hypertension1 : Systolic blood pressure of ≥140 mm Hg or diastolic blood pressure of ≥90 mm Hg.
The criteria adopted to diagnose significant proteinuria3,17,18: One 24-hour urine collection with a total protein excretion of 300 mg / 24 hours. The criteria adopted with reference to oedema1,2: Previous definitions included oedema, but this sign is nonspecific and is observed in many normotensive pregnant women. Thus, oedema is no longer considered part of the diagnostic criteria for preeclampsia. Pre-eclampsia patients may or may not have pathological oedema. The criteria adopted to diagnose high-risk serum uric acid level19: Values ≥6 mg/dl (360 µmol/l) was cut off level for high risk in our study.
Inclusion criteria: All patients diagnosed as pre-eclampsia as per the above criteria subject to their willingness to participate in the study after informed consent. Exclusion criteria: 1. History of chronic hypertension 2. Family history of hypertension or diabetes mellitus 3. Pre existing medical illness like heart disease, diabetes mellitus, renal diseases or thyroid disorders. 4. Hypertension before 20 weeks of gestation 5. Patients who are not willing to participate in the study. Method of study Out of all cases admitted with the diagnosis of pre-eclampsia, 60 were selected based upon fulfilling inclusion and exclusion criteria.
A detailed history of each patient was taken and complete general and obstetric examination was done. All findings were recorded in pre-designed proforma. Hyperten- sion and Proteinuria were diagnosed as per the criteria already described. For all patients included in the study all routine investigations including serum uric acid were done and recorded. For determination of serum uric acid two methods have been described: 1. Calorimetric method (Caraway’s method) and 2.
Enzymatic method. Calorimetric method is influenced by many factors in the procedure as well as many contaminating substances in the glassware etc. In the enzymatic method, enzyme uricase has been widely used for uric acid determinations because of its improved specificity20-22. Therefore, we used enzymatic method. All the patients were followed up until delivery and all maternal and foetal events were recorded. All complications of pre-eclampsia both maternal and foetal were statistically analysed to prove the predictive value of serum uric acid levels.
RESULTS AND OBSERVATIONS
Distribution according to the age of mothers: 18.3% of mothers were between the age group 18-21 years, 26.7% were between 22-25 years, 28.3% were between 26-29 years, and 26.7% were above 30 years (Table/Fig 2). Distribution according to Gravida: 60.0% of mothers were primi, 28.3% were second gravid, 8.3% were third gravid and 3.3% were fourth gravid (Table/Fig 3). Distribution according to Parity: 83.4% of 60 mothers were primi para, 8.3% were para 2, and 8.3% were para 3 (Table/ Fig 4). Distribution according to period of gestation: 28.3% were 37-38 weeks, 2.0% were 38-39 weeks, 33.3% were 39-40 weeks, 18.3% were 40-41 weeks of gestation (Table/Fig 5).
Mean and Standard Deviation of Blood Pressure, Serum Uric acid and Foetal outcome: The mean systolic was 146.33 and standard deviation 7.12. The mean diastolic was 95.67 and standard deviation 6.21. The mean uric acid was 5.25 and standard deviation 1.64. The mean foetal outcome of APGAR 1 minute was 4.05 and standard deviation 1.84. The mean foetal outcome of APGAR 5 minutes was 6.49 and standard deviation 1.19 (Table/Fig 6). Distribution of Mothers according to Urine Albumin: Urine albumin was 1+ in 26.7% of mothers, 2+ in 43.3% of mothers, 3+ in 26.7 % of mothers and 4+ in 3.3% of mothers (Table/Fig 7).
Distribution of Mothers according to Mode of Delivery: 83.3% of mothers had caesarean section, 6.7% of mothers had abnormal vaginal delivery, another 6.7% had normal vaginal delivery and 3.3% had forceps delivery (Table/Fig 8). Distribution of Mothers according to IUGR (intra uterine growth retardation) and IUD (intra uterine death): 79.4% of 60 mothers were admitted with IUGR, 14.7% of mothers were admitted with IUD and 5.9% of mothers were admitted with both IUGR and IUD (Table/Fig 9). Relationship between 1st min APGAR and Serum Uric Acid: 94.4% of babies under high-risk category had an APGAR of less than 5/10 in the 1st minute of their life, whereas 80.0% of the babies under no risk category had an APGAR of less than 5/10 in the 1st minute of their life. The difference in the first minute APGAR in the high risk and no risk category was not statistically significant at p value of 0.1798 (Table/Fig 10).
Relationship between 5th min APGAR and Serum Uric Acid: 55.6% of babies under high-risk category had an APGAR of less than 5/10 in the 5th minute of their life, whereas 11.9% of the babies under no risk category had an APGAR of less than 5/10 in the 5th minute of their life (Table/Fig 11). The difference in the 5th minute APGAR in the high risk and no risk category was statistically significant at p value of 0.001. From this table infers that the mothers whose serum uric acid was more than 6 mg/dl had 4-5 times increased risk of having APGAR of less than 5/10 at 5th min when compared to mothers with serum uric acid less than 6mg/dl. Maternal complications: 4 out of 42 women (9.52%) with serum uric acid ≥ 6mg/dl had maternal complications and 7 out of 18 women with serum uric acid <6mg/dl had maternal complications with a statistically significant p value of 0.01 (Table/Fig 12).
Types of Maternal Complications of Pre-eclampsia: 9.1% of mothers developed HELLP, 18.2% of mothers developed Ascites, 27.3% of mothers developed Eclampsia and 45.5% of mothers developed Abruption (Table/Fig 13). Serum Uric Acid and Baby Weight: Considering less than 2.5 Kg as low birth weight serum uric acid levels of more than 5.5 are associated with significant low birth weight (p value of 0.01) which is statistically significant (Table/Fig 14). Stepwise regression analysis of predictive value of Serum Uric Acid: Serum uric acid has significantly contributed for predicting the foetal outcome compared to maternal outcome. The predictive value of the variable separately is 0.01. Altogether, the above computations clearly state that serum uric acid will be highly predictive of foetal complications as compared to maternal complications (Table/Fig 15).
DISCUSSION Total number of patients fulfilling all inclusion criteria and having given consent for the study were 60 (n=60). Age and gravida/para status: According to Mac Gillvary23 the relationship of the maternal age and pre-eclampsia incidence gives a ’J’ shaped curve with increased incidence among young primi gravida and markedly increased among older primi gravid.
According to Duckitt K et al24, about 60% of the patients in pre-eclampsia group were primigravdae. This correlates well with our present study. In our present study 17 women were between 26-39 years (28.3%) and 16 women were between 22-25 and less than 30 years (26.7%) and only 11women were between 18-21 years (18.3%). 36 (60%) were primigravidae and 24 (40%) were multi gravidae; 83.4% were primi para, 8.3% were second para and 8.3 were third para. Maternal outcome and serum uric acid: According to Disha Sahijuani et al25 10 out of 50 women (20%) with uric acid 6mg/dl and only 11.9% of them with APGAR less than 5/10 at fifth minute were under low risk category.
The difference in fifth minute APGAR in the high risk and no risk group was statistically significant at p value of 0.001. It is inferred that mothers whose serum uric acid was high had 4-5 times increased chances of delivering baby with less than 5/10 APGAR at fifth minute when compared to mothers whose serum uric acid was normal. Even though the above inferences in our study are, in favour serum uric acid levels ≥6mg/dl is predictive of both maternal and foetal complications at p value of 0.001 and 0.01 respectively, the step wise regression analysis infers that serum uric acid will be highly predictive of foetal complications (p value of 0.01) as compared to maternal complications (p value of 0.42).
In systematic review conducted by Thangaratinam et al27, on 17 studies26,24-43 with sample size ranging from 14-504 pre-eclampsia women, it was concluded that serum uric acid is a poor predictor of maternal and foetal complications in women with pre-eclampsia. Several other studies (six studies) have reported a positive correlation between elevated maternal serum uric acid and adverse maternal and foetal outcomes9-15.
CONCLUSION In the past 17 studies with sample sizes ranging from 14 to 504 have concluded that serum uric acid is poor predictor of foetal and maternal complications of pre-eclampsia. Six other studies have reported a positive correlation between elevated maternal serum uric acid and adverse maternal and foetal outcomes. However, our study with a sample size of 60 has proved that serum uric acid is statistically significant predictor (p value 0.01) of foetal complications of pre-eclampsia even though not of maternal complications (p value 0.42). Further studies with bigger sample size may substantiate our conclusion.
ACKNOWLEDGEMENT Authors duly thank Dr. S. Viswanathan, Professor and Head, department of obstetrics and gynaecology, and Dr. S. Balasubramaniyan, Dean, Raja Muthiah Medical College and Hospital, Annamalai University, Annamalai Nagar, Chidabmbaram, India, for permitting us to publish the contents of PG Dissertation of Dr. A. Ramana priya, as an article in IJCRR. Authors also acknowledge Dr. K. Lalitha Professor obstetrics & gynaecology, Raja Muthiah Medical College and Hospital, Annamalai University, Annamalai Nagar, Chidabmbaram, India, for her immense help as Guide to Dr. A. Ramana priya, in accomplishing her dissertation work. Authors also acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. Authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Source of funding: Nil Conflict of interest: All authors declare that there is no conflict of interest.
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