though the exact incidence is unknown , it ranges from 3 - 10% in nulliparous population . it is a significant public health threat globally contributing greatly to maternal and perinatal mortality and morbidity .
extensive changes occur in the kidneys as part of the end - organ damage in preeclampsia .
proteinuria occurs as a consequence of reduction in the integrity of glomerular barrier or reduced tubular reabsorption .
it remains an important objective criterion for diagnosis of preeclampsia and has been used to classify the severity as well as to predict adverse fetomaternal outcomes in preeclampsia . among the various methods available to quantify proteinuria ,
alternative methods like a spot urine sample protein - creatinine ( p / c ) ratio avoid the influence of variations in urinary solute concentrations and can reduce the delay in diagnosis and management of preeclamptic patients .
though , serum uric acid level is of limited use in the initial diagnosis of preeclampsia , many investigators have shown that it correlates well with the disease severity . in this study , we have tried to correlate spot urine p / c ratio with 24-h urine protein estimation and test its diagnostic accuracy for detecting significant proteinuria .
we have also correlated spot urine p / c ratio with serum uric acid levels and tried to analyze the association between proteinuria and hyperuricemia with adverse fetomaternal outcomes in preeclamptic women .
this observational correlation clinical study was conducted after obtaining clearance from the hospital ethics committee .
this was a prospective study conducted between november 2010 and may 2012 , among pregnant women admitted to the hospital with a suspicion of preeclampsia .
primigravida with singleton pregnancy , with cephalic presentation , and a diagnosis of preeclampsia were included in the study .
preeclampsia was diagnosed when blood pressure was 140/90 mm hg or more , on two occasions , at least 4 h apart , or a single diastolic reading of  110 mm hg after the 20 week of pregnancy , and the presence of proteinuria of  1 + as detected by dipstick urine analysis .
women with previous renal disease , chronic hypertension , urinary tract infection , pathological vaginal discharge , and those who required delivery before the completion of a 24-h urine sample were excluded from the study .
a total of 75 pregnant women who satisfied the inclusion and exclusion criteria were recruited after informed written consent for participation .
participants were asked to collect a random midstream urine sample for estimating the spot urine p / c ratio .
they were then instructed to collect the 24-h urine starting from the second urine sample in the morning ( i.e. , after discarding the first morning specimen ) till the first urine sample the next day morning .
the urine p / c ratio was obtained by dividing the urinary protein concentration by the urinary creatinine concentration .
urine protein was measured by the urinary - cerebrospinal fluid protein method , which is an adaptation of the pyrogallol red - molybdate method .
urine creatinine was measured by the crea method , which is a modification of the jaffe 's reaction .
serum uric acid was assessed using automated photospectrometric assay approved by the international federation of clinical chemistry for all the patients .
all the patients were followed up till their delivery and the various parameters for maternal and fetal outcomes were noted .
fetal outcomes noted were apgar scores at 1 and 5 min , neonatal intensive care unit ( nicu ) admission , birth weight , any other neonatal complications like neonatal sepsis , stillbirth , seizures , and so on .
adverse maternal outcomes were defined as any maternal complications like abruption , eclampsia , postpartum hemorrhage , disseminated intravascular coagulation ( dic ) , hemolysis , elevated liver enzymes , and low platelets ( hellp ) syndrome , and so on .
r was used to correlate between spot urine p / c ratio , 24-h urine protein and serum uric acid levels .
p was used to study the levels of spot urine p / c ratio , 24-h urine protein and serum uric acid level in predicting the fetomaternal outcomes .
receiver operating characteristic ( roc ) curve analysis was done to evaluate the diagnostic accuracy of spot urine p / c ratio to detect significant proteinuria ( > 300 mg / day ) .
the statistical software sas 9.2 was used for the analysis of the data and microsoft word and excel were used to generate graphs , tables , and so on .
a total of 75 pregnant women with preeclampsia were recruited in the study after meeting our criteria .
of these , 73.3% had mild preeclampsia ( proteinuria of 1 + using urine dipstick analysis ) and 26.7% had severe preeclampsia ( proteinuria of 2 + with urine dipstick ) .
[ table 1 ] shows the distribution of the patients according to their 24-h urine protein , spot urine p / c ratio , and serum uric acid levels .
the pearson 's correlation test showed a positive correlation between 24-h urine protein and spot urine p / c ratio ( r = 0.373 ) with a p = 0.001 which was strongly significant [ table 2 ] .
scatter diagram demonstrated a linear correlation between spot urine p / c ratio and 24-h urine protein [ figure 2 ] .
roc curve analysis showed that the optimal cut - off value of spot urine p / c ratio to detect significant proteinuria ( > 300 mg / day ) was > 0.6 , at which , the sensitivity was 73.53% and specificity was 65.85% .
area under curve ( auc ) was 0.799 ( good test ) [ figure 3 ] . though spot urine p / c ratio had a high sensitivity of 96.9% , but specificity was only 19% at cut - off value of spot urine p / c > 0.3 for significant proteinuria .
a statistically significant and direct correlation was also found between serum uric acid and spot urine p / c ratio ( r = 0.355 , p = 0.002 ) [ table 2 ] .
demographic data : ( a ) age in years , ( b ) period of gestation and ( c ) region - wise distribution distribution of patients according to 24-h urine protein , spot protein / creatinine ratio , and serum uric acid levels pearson 's correlation between 24-h urine protein , spot urine protein / creatinine ratio , and serum uric acid scatter diagram showing correlation between spot urine protein / creatinine ratio and 24-hour urine protein as well as between serum uric acid and 24-hour urine protein receiver operating characteristic curves of spot urine protein/ creatinine ratio ( bold curve ) in reference to 24-hour urine protein ( upper dashed curve ) and serum uric acid ( lower dashed curve ) .
the cut - off value of spot p / c ratio is > 0.6 , for which sensitivity is 73.53% and specificity is 65.85% with roc area under curve of 0.799 ( good test ) though there was no statistically significant association between proteinuria and hyperuricemia with the various fetal and maternal outcome parameters studied , as shown in tables 3 , 4 , and 5 , we had three maternal complications , namely , abruptio placentae , intrapartum eclampsia , and hellp syndrome , which occurred in patients with significant proteinuria and elevated uric acid levels .
there were 11 intrauterine growth restrictions ( iugrs ) in our study and it was most of the time ( 89% ) associated with significant proteinuria .
a stillbirth occurred in a patient with severe preeclampsia , induced at 30 weeks , who had significant proteinuria ( 534 g / day ) , a spot p / c ratio of 0.9 and normal serum uric acid levels .
fetomaternal outcomes with 24-h urine protein fetomaternal outcomes with spot urine protein / creatinine ratio fetomaternal outcomes with serum uric acid
preeclampsia is a multisystemic disorder with endothelial dysfunction which affects 3 - 5% of all pregnancies and contributes greatly to fetomaternal morbidity and mortality .
renal dysfunction leading to proteinuria ( a diagnostic hallmark of preeclampsia ) , along with hyperuricemia have been used to predict adverse pregnancy outcomes .
24-h urine protein estimation has been considered the gold standard for testing proteinuria but has the disadvantage of consuming time , delaying diagnosis , and thus delaying initiation of appropriate management .
alternative testing methods like p / c ratio on a single random urine sample have correlated well with the gold standard .
this study was conducted from november 2010-may 2012 , to estimate the diagnostic accuracy of spot p / c ratio , to evaluate efficacy of 24-h urinary protein , spot urine p / c ratio and serum uric acid in predicting the outcomes in preeclampsia and to correlate spot urine p / c ratio with serum uric acid levels . in our study , the mean age was 25.35 years and the mean gestational period was 36.9 weeks among 75 preeclamptic women .
we found a moderate correlation between 24-h urine protein and spot urine p / c ratio which was statistically significant ( r = 0.373 , p < 0.001 ) .
the roc curve analysis revealed a sensitivity of 73.53% and specificity of 65.85% with auc 0.799 ( good test ) for a cut - off value of spot
p / c > 0.6 to detect significant proteinuria . in a similar study done by aggarwal et al . , in 120 preeclamptic women , the mean age was 26 years and mean gestational age was 32 weeks .
they reported a significant association between the two tests with a correlation coefficient of r = 0.596 ( p
< 0.01 ) and the sensitivity and specificity of spot p / c at a cut - off value > 1.14 of 72% and 75% , respectively .
but they observed that the values of the spot urine p / c correlated well at higher levels of proteinuria .
thus , they concluded that the test could not rule out mild preeclampsia , and hence should not be used to replace 24-h urine protein estimation .
wheeler et al . , conducted a study among 126 patients admitted for evaluation of preeclampsia and reported a strong correlation of random spot urine p / c ratio with 24-h urine protein levels ( pearson 's r = 0.88 ) .
the optimal p / c cutoff was 0.21 ( 300 mg per 24 h ) and 3.0 ( 5000 mg per 24 h ) .
auc was 0.86 for cut - off values of 0.21 and 1.0 for cut - off values of 3.0 .
they concluded that though there is a strong association between the spot urine p / c ratio and 24-h urine protein excretion , the former lacks the ability to measure proteinuria quantitatively .
other reports have given conflicting results and report that 24-h urine collection should remain the standard for evaluation of preeclampsia .
durnwald and mercer in their comparative study between 24-h urine protein and spot urine p / c ratio among 220 preeclamptic women had a mean age of 26.1 years and gestational age of 36.5 weeks .
they reported a poor correlation with coefficient of 0.41 between 24-h urine and spot urine p / c ratio .
the roc analysis revealed no clear shoulder although the auc was 0.8 with a sensitivity of 55.8% and specificity of 81% at a cut - off value of 0.3 for spot urine p / c ratio .
morris et al . , in their systematic review and meta - analysis concluded that on an average , across all studies the optimal threshold of spot p / c ratio to detect significant proteinuria is between 0.30 and 0.35 , relating to sensitivity and specificity values above 75% .
proteinuria in preeclampsia occurs due to altered glomerular permeability and/or changes in tubular reabsorption of filtered proteins .
the severity of proteinuria has been regarded as a predictor for adverse maternal and fetal outcomes . a 24-h urine protein greater than 300 mg has been considered to be significant proteinuria . in our study ,
incidence of very low birth weight ( < 1500 g ) increased from 9.8% to 17.6% as the 24-h urine protein exceeded 300 mg .
nicu admission increased from 19.3% to 38.2% and fetal complications like iugr and neonatal sepsis from 9.8 - 26.5% at 24-h urine protein values of 300 mg or more .
there was one stillborn when the value of 24-h urine was more than 300 mg . there were three maternal complications namely , one abruptio placentae , one intrapartum eclampsia , and one hellp syndrome , all occurring when 24-h urine protein was > 300 mg .
but overall , the differences in maternal and fetal outcomes related to 24-h urine protein levels greater than or less than 300 mg did not attain statistical significance .
similar findings were reflected in the prediction of adverse fetomaternal outcomes using spot p / c ratio .
there was no nicu admission , very low birth weights , fetal complications in women with spot p / c < 0.3 .
whereas 15.2% had very low birth weight , 37.95% had nicu admission and 19.7% had fetal complications with spot urine p / c > 0.3 .
all the three maternal complications were present when spot urine p / c was > 0.3 . but none of the fetal and maternal parameters had significant association with spot p / c .
literature search revealed only one study which compared spot urine p / c in random urine samples with adverse outcomes in hypertensive pregnant women .
this study done by martins costa et al . , retrieved the medical charts of 370 hypertensive pregnant women and divided them into three groups based on the spot urine p / c values ( group 1 : < 0.3 , group 2 : 0.3 - 1.99 , group 3 2.0 ) . they compared the groups with composite maternal and perinatal outcomes like , dic , hellp , eclampsia , thrombocytopenia , neonatal sepsis , perinatal death , and small for gestational age .
they reported that at random spot urine p / c values > 0.3 , there was a high probability of having unfavourable maternal and fetal clinical outcomes , but additional increments were not associated with worsening of such outcomes , indicating the usefulness of the test to be diagnostic but not as a monitor of clinical worsening .
newman et al . , concluded in their study that women with preeclampsia and massive proteinuria did not have increased maternal morbidity compared with women with severe or mild proteinuria .
a systematic review of 16 studies for estimation of proteinuria as a predictor of complications of preeclampsia concluded that measure of proteinuria is a poor predictor of either maternal or fetal complications .
, questioned the commonly practised management decisions based on severity of proteinuria in preeclamptic women and highlighted the need for large well - designed prospective studies to address this important issue .
the utility of serum uric acid as a marker of severity of preeclampsia has been substantiated by several studies .
yassaee found a strong correlation between apgar scores less than 7 and serum uric acid levels 6 mg / dl . in our study
there were five iugrs ( 45% ) in women who had uric acid levels more than 5.5 mg / dl and the same number in uric acid levels 3.5 - 5.5 mg / dl .
we observed no differences in the occurrence of fetal complications , nicu admissions between the levels of uric acid 3.5 - 5.5 and > 5.5 mg / dl .
yassaee reported an ( intra - uterine death ) iud rate of 22% at uric acid levels more than 6 mg / dl . in the present study , no still births were found at levels > 5.5mg / dl with only one stillbirth at uric acid level 3.5 - 5.5 mg / dl ( 2.3% ) .
overall , we found no statistical significance between serum uric acid levels and the various parameters of fetal outcome in our study .
the three maternal complications in our study , namely , abruptio placentae , hellp , and intrapartum eclampsia occurred when the uric acid levels were > 5.5 mg / dl , and we thought , this had a suggestive significance ( p < 0.063 ) .
yaasaee noted that 22% had eclampsia with serum uric acid > 6mg / dl in their study .
they showed a strong significant ( p < 0.01 ) relationship of hyperuricemia with maternal outcomes in their study . a retrospective analysis by parrish et al .
, showed adverse maternal outcomes in 15.3% of 258 persons in their cohort study . in the present study , adverse maternal outcomes occurred in only 4% of the 75 patients studied . in a systematic review of accuracy of serum uric acid in predicting complications of preeclampsia , thangaratinam et al . ,
he concluded that serum uric acid is a poor predictor of maternal and fetal complications in women with preeclampsia . in this study
as well , we could not confirm the association between serum uric acid and fetomaternal outcomes .
the magnitude of proteinuria and hyperuricemia has been correlated with the severity of renal histological finding of glomerular endotheliosis .
if so , is there any association between levels of proteinuria and serum uric acid ?
we tried to correlate proteinuria using spot p / c and 24-h urine protein with serum uric acid levels .
correlation coefficients showed a moderate correlation with urine spot p / c ratio and uric acid ( r = 0.355 , p < 0.002 ) and poor correlation with 24-h urine protein and uric acid level ( r = 0.118 , p = 314 ) .
however , no studies have been reported till date regarding this and the sample size is very small to generalize the results .
there was no blinding of the results of spot p / c ratio which might have influenced decisions regarding management of patients to avoid complications .
as preeclamptic women on drugs were not excluded , the influence of these drugs on parameters studied might have been obscured .
there were no patients with proteinuria more than 1 g , so we could not assess the impact of high levels of proteinuria on pregnancy outcomes .
in the present study , we found a moderate correlation between 24-h urine protein and spot urine p / c ratio which was statistically significant ( r = 0.373 , p < 0.001 ) .
the optimal cut - off value of spot urine p / c ratio for significant proteinuria was > 0.6 at which the sensitivity was 73.53% and specificity was 65.85% .
the roc curve analysis for spot urine p / c ratio had an auc of 0.799 ( good test ) .
there was a moderate correlation between spot urine p / c ratio and serum uric acid ( r = 0.355 , p < 0.002 ) .
there was no statistically significant association between proteinuria and serum uric acid with fetomaternal outcomes in preeclampsia .
 background : it is well - known that estimation of 24-h urine protein and spot urine protein / creatinine ( p / c ) ratio are commonly performed investigations to assess proteinuria in preeclamptic women . 
 serum uric acid has been shown to correlate well with disease severity in preeclampsia.materials and methods : a total of 24-h urine protein estimation , spot urine p / c ratio , and serum uric acid measurements were carried out in 75 pregnant preeclamptic women and the correlation between these investigations , as also the association between proteinuria and hyperuricemia with adverse fetomaternal outcomes were studied.results:pearson's correlation test showed a positive correlation between 24-h urine protein and spot urine p / c ratio . 
 a statistically significant and direct correlation was also found between serum uric acid and spot urine p / c ratio , while there was no statistically significant difference between proteinuria and hyperuricemia with respect to the various fetal and maternal outcome parameters studied.conclusion:in the present study , we found a moderate correlation between 24-h urine protein and spot urine p / c ratio . 
 there was a moderate correlation between spot urine p / c ratio and uric acid , while there was no statistical significance of the association between proteinuria and uric acid with fetomaternal outcomes in preeclampsia . 
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION