|Year : 2017 | Volume
| Issue : 2 | Page : 58-62
Diagnostic accuracy of spot albumin creatinine ratio and its association with fetomaternal outcome in preeclampsia and eclampsia
Rekha Sachan1, Munna Lal Patel2, Pushpalata Sachan3, Radhey Shyam4, Pratima Verma1, Soniya Dheeman1
1 Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Internal Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Physiology, Career Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
4 Department of Geriatric and Mental Health, King George's Medical University, Lucknow, Uttar Pradesh, India
|Date of Web Publication||27-Nov-2017|
Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Hypertensive disorders in pregnancy are one of the leading causes of maternal and perinatal mortality. Proteinuria is one of the common and important features of preeclampsia. To evaluate the diagnostic accuracy of albumin-creatinine ratio (ACR) in woman with preeclampsia and eclampsia and examine the association between ACR and fetomaternal outcome. Materials and Methods: Prospective study carried out over a period of 1 year in the Department of Obstetrics and Gynaecology, after informed consent and ethical clearance total ninety pregnant women from gestational age 20 to 40 weeks were enrolled, including, thirty preeclampsia, thirty antepartum eclampsia, considered as cases and thirty normotensive pregnant women as controls. Preeclampsia was defined as per National High Blood Pressure Education Program 2000 working group. All patients were asked for a spot midstream urine sample, followed by 24 h urine collection. Urinary protein was estimated by the sulfosalicylic acid method and creatinine by the Jaffe's method. The urinary ACR was determined by automated analyzer. Results: Mean value of urinary ACR of controls was significantly lower (0.103 ± 0.037) as compared to both groups. On comparing between groups the difference was significant (<0.001), a strong correlation between urinary ACR levels and 24 h urinary proteins was observed. Conclusion: In our study, an association of raised ACR values with severity of disease as well as with adverse fetomaternal outcome was observed.
Keywords: Albumin creatinine ratio, preeclampsia, urinary protein
|How to cite this article:|
Sachan R, Patel ML, Sachan P, Shyam R, Verma P, Dheeman S. Diagnostic accuracy of spot albumin creatinine ratio and its association with fetomaternal outcome in preeclampsia and eclampsia. Niger Med J 2017;58:58-62
|How to cite this URL:|
Sachan R, Patel ML, Sachan P, Shyam R, Verma P, Dheeman S. Diagnostic accuracy of spot albumin creatinine ratio and its association with fetomaternal outcome in preeclampsia and eclampsia. Niger Med J [serial online] 2017 [cited 2019 Feb 18];58:58-62. Available from: http://www.nigeriamedj.com/text.asp?2017/58/2/58/219345
| Introduction|| |
Hypertensive disorders in pregnancy are one of the leading causes of maternal and perinatal morbidity and mortality across the world. It complicates approximately 10% of pregnancies. Incidence has increased by 25% in the United States during the past two decades  and estimated maternal deaths are 50,000–60,000 per year worldwide., Proteinuria is one of the common and important features of preeclampsia. Proteinuria ≥300 mg/24 h urine collection or Dipstick reading of 1+ is required for the diagnosis of preeclampsia. However, now there is modification in guidelines and recent recommendation state that it is not the essential component for the diagnosis of preeclampsia.
Urine dipstick method is a semi-quantitative colorimetric test. It is inexpensive, easily available and simple to do. It is very commonly performed test for screening of proteinuria, but it should be used only if other quantitative methods are not available. It has high false positive rate, so it is always followed by other quantitative test. Quantification of proteinuria can be done by other methods like 24 h urine collection and protein estimation. This is the traditional method and considered as Gold standard, but it has many drawbacks. It is time-consuming, inconvenient, and inaccurate because of over or under collection of urine.
Protein to creatinine (PC) ratio is an accurate, rapid, convenient method and over a dozen of studies ,, and three metaanalyses ,, had validated it. A spot urine PC ratio above 0.7 mg protein/mg creatinine is strongly suggestive of significant proteinuria.
Albumin-creatinine ratio (ACR) like PC ratio, it is measured using a random spot urine specimen. It has increased sensitivity as compared to PC ratio. It also has the advantage that it can be performed using automated analyzer. Thus, this test is too rapid to be done on the same day and can be carried out in women attending antenatal clinic.,,
Several international organizations such as International Society for the Study of Hypertension in pregnancy, the Society of Obstetric Medicine of Australia and New Zealand, and the Society of Obstetricians and Gynaecologist of Canada , had approved the spot urine ACR for detection of proteinuria but this is not accepted by all international bodies such as National High Blood Pressure Education Program (NHBPEP) 2000 Working Group.
Very few studies ,,,, have been done to evaluate the association between severity of proteinuria and fetomaternal outcome.
The aim of the study is to evaluate the diagnostic accuracy of ACR in woman with preeclampsia and eclampsia and association between ACR and fetomaternal outcome.
| Materials and Methods|| |
This is a prospective observational study carried out over a period of 1 year in Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow.
After informed consent and ethical clearance total ninety pregnant women from gestational age 20 to 40 weeks were enrolled, including, thirty preeclampsia, thirty antepartum eclampsia, considered as cases and thirty normotensive pregnant women taken as controls.
Preeclampsia was defined as per NHBPEP2000 working group, resting hypertension >140/90 mmHg after 20th weeks of pregnancy. Eclampsia is defined as preeclampsia with seizure.
Women with multiple pregnancy, chronic kidney disease, liver disease, cardiovascular disease, collagen vascular disease, chronic hypertension, diabetes, neoplasm, with major fetal anomaly, history of smoking, and using alcohol were excluded from the study.
Adverse maternal outcome was defined in terms of occurrence of preterm delivery, changes in fundus on eye examination and maternal mortality.
Adverse fetal outcome was defined as low birth weight babies, intrauterine fetal death, low Apgar score, neonatal resuscitation, neonatal death, and Neonatal Intensive Care Unit (NICU) admission.
After taking informed consent and ethical clearance, all patients were asked for a spot mid-stream urine sample, followed by 24 h urine collection. Urinary protein was estimated by the sulfosalicylic acid method and creatinine by the Jaffe's method. The urinary ACR was determined by automated analyzer and data were expressed as mg/dl.
Pearson correlation test was used to detect a correlation between the ACR in the spot urine samples and 24 h urinary protein. Chi-square test, Student's t-test, and ANOVA were used for analysis of data.
| Results|| |
A total of ninety pregnant women were included in the study. These were classified into three groups, Group I - Controls, normotensive pregnant women (30), Group II - Preeclampsia (30), Group IIa - Mild preeclampsia (15), Group IIb - Severe preeclampsia (15), and Group III - Eclampsia (30).
Mean urinary ACR level was minimum in controls, and maximum in eclampsia and difference among groups was statistically significant.
Mean value of urinary ACR of controls was significantly lower (0.103 ± 0.037) as compared to both groups preeclampsia and eclampsia (1.901 ± 1.121 and 2.884 ± 1.499), respectively. On comparing between groups, the difference was significant (<0.001), mean urinary ACR of eclampsia was found to be significantly higher as compared to that of preeclampsia [Table 1].
|Table 1: Comparison of mean urinary albumin creatinine ratio in different study groups|
Click here to view
When urinary ACR was compared between mild preeclampsia and severe preeclampsia, the difference between groups was found statistically significant (P< 0.001) [Table 2].
|Table 2: Comparison of mean urinary albumin creatinine ratio exploring association with severity of disease|
Click here to view
When we analyzed a correlation between urinary ACR levels and 24 h urinary proteins, a strong correlation was observed, for which value of Pearson's correlation was found to be 0.986 (P< 0.001) [Figure 1]. As the disease severity (Group I to Group III) increased 24-hr urinary protein as well as albumin creatinine ratio was also increased and this increment after comparison between different groups was statistically significant [Table 3].
|Figure 1: Pearson's correlation value = 0.986 (P < 0.001); (very strong correlation)|
Click here to view
|Table 3: Albumin creatinine ratio and 24 h urinary protein between group comparison (Student's t-test)|
Click here to view
In the present study, association of urinary ACR with fetal outcome was evaluated, and it was found that mothers who had a significant increase in urinary ACR levels delivered low birth weight babies and also suffered with intrauterine fetal demise and this association was significant (P< 0.001). In cases whose babies had low Apgar scores and needed resuscitation, and NNU admission had significantly higher urinary ACR (P< 0.05). Neonatal deaths were also associated with raised maternal urinary ACR as compared to healthy neonates but this difference was statistically not significant [Table 4].
|Table 4: Association between albumin creatinine ratio levels and fetal outcome|
Click here to view
Although the levels of ACR were higher with preterm vaginal birth, this association was not significant. Total four women expired during the study and mean ACR level of these women were almost doubled than alive women, but this association was statistically nonsignificant (P > 0.05). Similarly, cases with high grade of fundus changes and need for magnesium sulfate administration had significantly higher urinary ACR [Table 5].
|Table 5: Association between albumin creatinine ratio levels and maternal outcome|
Click here to view
| Discussion|| |
Hypertensive disorders in pregnancy stand out to be one of the leading causes of maternal and neonatal morbidity and mortality. Timely and effective intervention has utmost importance in the prevention of these complications. Proteinuria has been an important constituent of preeclampsia.
Since long time Gold standard test for detection of proteinuria was the estimation of protein after 24 h of urine collection. However, this test is time consuming, cumbersome, and causes delay in decision-making. Spot urinary ACR can substitute this test because this test is rapid, easy to do and accurate.
In this study, strong correlation (r = 0.986) was observed between the spot ACR and the 24 h urinary protein estimation. Similar result was achieved by many studies.
Although the diagnosis of severe preeclampsia is no longer dependent on the presence of proteinuria, women with hypertensive disorders of pregnancy with increasing ACR might be considered serious and we should not delay the management of preeclampsia in these patients.
Massive proteinuria (>5 g) has been eliminated from the consideration of grade of severity of preeclampsia. This result was concluded on the basis of two important facts, first one is that few studies ,, reported that severity of proteinuria is only weakly associated with adverse maternal and neonatal outcome and should not be used to decide the management guideline but our study, in contrast, reported significant association of ACR with adverse fetomaternal outcome.
Second, proteinuria may be absent in up to 10% of women with preeclampsia and 20% of women with eclampsia at the time of initial presentation.,
With regard to preeclampsia, one study had reported that microalbuminuria might be a good predictor of this condition with a high sensitivity but a low positive predictive value. In contrast, another study reported that microalbuminuria is not a good predictor of preeclampsia.
Other author had reported that microalbuminuria early in the third trimester of pregnancy is a good predictor of hypertensive complications in pregnancy and birth weight of the babies, but it cannot predict intrauterine growth - restriction (IUGR) and neonatal outcome.
Other proposed that the appearance of clinical proteinuria in preeclampsia is preceded by a microalbuminuria. However, these authors observed this microalbuminuria (determined during 11–13 weeks of pregnancy) in 55% of normal pregnancies and only 75% of pregnancies that complicated by preeclampsia.
As per one study incidence of induced labor (P = 0.045) and cesarean section (P< 0.001) was more associated with microalbuminuria group, which could be due to the significant association of maternal complication (P< 0.001) in the same group. In our study, it was also found that adverse neonatal outcome like fetal complication, IUGR was significantly more in babies of microalbuminuria group (P = 0.010*). It was also found that prematurity, low birth weight, low Apgar score, and more incidence of NICU admission in babies of pregnant women with microalbuminuria.
Another one more study which was in consensus with the results of our study.
Gangaram et al. compared the diagnostic value of the ACR with that of the 24-h urine protein test among pregnant women with hypertension. They reported that the value of the two tests in this context was the same and concluded that measurement of the micro ACR may be a good substitute for a random urine protein test.
However, the relationship of maternal complications such as preeclampsia and preterm labor with microalbuminuria is still controversial. Further research with a large sample size is needed to establish the relationship between microalbuminuria and maternal complication. In one study, women with ACR >312 mg albumin/g creatinine at 17–20 weeks of gestation were found to be at 8-fold higher risk of developing preeclampsia.
| Conclusion|| |
A spot ACR in mid-stream urine might be considered for replacement of 24 h urine protein excretion in the evaluation of preeclampsia and eclampsia. This test also has the potential to replace urinary dipstick method in routine antenatal clinic, but more data are required. In our study, association of raised ACR values with severity of disease as well as with adverse fetomaternal outcome was observed. However, limitation of our study is small sample size, so more studies with good sample size are required to validate these results. It appears that ACR could be very useful test in near future not only for predicting the development of preeclampsia, but it also predict its severity and fetomaternal outcome.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;122:1122-31.
Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987-2004. Am J Hypertens 2008;21:521-6.
Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. Br J Obstet Gynaecol 1992;99:547-53.
Waugh JJ, Clark TJ, Divakaran TG, Khan KS, Kilby MD. Accuracy of urinalysis dipstick techniques in predicting significant proteinuria in pregnancy. Obstet Gynecol 2004;103:769-77.
Côté AM, Firoz T, Mattman A, Lam EM, von Dadelszen P, Magee LA. The 24-hour urine collection: Gold standard or historical practice? Am J Obstet Gynecol 2008;199:625.e1-6.
Aggarwal N, Suri V, Soni S, Chopra V, Kohli HS. A prospective comparison of random urine protein-creatinine ratio vs 24-hour urine protein in women with preeclampsia. Medscape J Med 2008;10:98.
Kyle PM, Fielder JN, Pullar B, Horwood LJ, Moore MP. Comparison of methods to identify significant proteinuria in pregnancy in the outpatient setting. BJOG 2008;115:523-7.
Stout MJ, Scifres CM, Stamilio DM. Diagnostic utility of urine protein-to-creatinine ratio for identifying proteinuria in pregnancy. J Matern Fetal Neonatal Med 2013;26:66-70.
Côté AM, Brown MA, Lam E, von Dadelszen P, Firoz T, Liston RM, et al.
Diagnostic accuracy of urinary spot protein: Creatinine ratio for proteinuria in hypertensive pregnant women: Systematic review. BMJ 2008;336:1003-6.
Papanna R, Mann LK, Kouides RW, Glantz JC. Protein/creatinine ratio in preeclampsia: A systematic review. Obstet Gynecol 2008;112:135-44.
Morris RK, Riley RD, Doug M, Deeks JJ, Kilby MD. Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: Systematic review and meta-analysis. BMJ 2012;345:e4342.
Wilkinson C, Lappin D, Vellinga A, Heneghan HM, O'Hara R, Monaghan J. Spot urinary protein analysis for excluding significant proteinuria in pregnancy. J Obstet Gynaecol 2013;33:24-7.
Nisell H, Trygg M, Bäck R. Urine albumin/creatinine ratio for the assessment of albuminuria in pregnancy hypertension. Acta Obstet Gynecol Scand 2006;85:1327-30.
Gangaram R, Naicker M, Moodley J. Comparison of pregnancy outcomes in women with hypertensive disorders of pregnancy using 24-hour urinary protein and urinary microalbumin to creatinine ratio. Int J Gynaecol Obstet 2009;107:19-22.
Lowe SA, Brown MA, Dekker GA, Gatt S, McLintock CK, McMahon LP, et al.
Guidelines for the management of hypertensive disorders of pregnancy 2008. Aust N
Z J Obstet Gynaecol 2009;49:242-6.
Magee LA, Helewa M, Moutquin JM, von Dadelszen P; Hypertension Guideline Committee; Strategic Training Initiative in Research in the Reproductive Health Sciences (STIRRHS) Scholars. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. J Obstet Gynaecol Can 2008;30 3 Suppl: S1-48.
Lindheimer MD, Taler SJ, Cunningham FG. Hypertension in pregnancy. J Am Soc Hypertens 2008;2:484-94.
Lindheimer MD, Taler SJ, Cunningham FG; American Society of Hypertension. ASH position paper: Hypertension in pregnancy. J Clin Hypertens (Greenwich) 2009;11:214-25.
Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000;183:S1-S22.
von Dadelszen P, Payne B, Li J, Ansermino JM, Broughton Pipkin F, Côté AM, et al.
Prediction of adverse maternal outcomes in pre-eclampsia: Development and validation of the full PIERS model. Lancet 2011;377:219-27.
Payne B, Magee LA, Côté AM, Hutcheon JA, Li J, Kyle PM, et al.
PIERS proteinuria: Relationship with adverse maternal and perinatal outcome. J Obstet Gynaecol Can 2011;33:588-97.
van der Tuuk K, Holswilder-Olde Scholtenhuis MA, Koopmans CM, van den Akker ES, Pernet PJ, Ribbert LS, et al.
Prediction of neonatal outcome in women with gestational hypertension or mild preeclampsia after 36 weeks of gestation. J Matern Fetal Neonatal Med 2015;28:783-9.
Thornton CE, Makris A, Ogle RF, Tooher JM, Hennessy A. Role of proteinuria in defining pre-eclampsia: Clinical outcomes for women and babies. Clin Exp Pharmacol Physiol 2010;37:466-70.
Sibai BM. Eclampsia. VI. Maternal-perinatal outcome in 254 consecutive cases. Am J Obstet Gynecol 1990;163:1049-54.
Huang Q, Gao Y, Yu Y, Wang W, Wang S, Zhong M. Urinary spot albumin:creatinine ratio for documenting proteinuria in women with preeclampsia. Rev Obstet Gynecol 2012;5:9-15.
Salako BL, Olayemi O, Odukogbe AT, Adedapo KS, Aimakhu CO, Alu FE, et al.
Microalbuminuria in pregnancy as a predictor of preeclampsia and eclampsia. West Afr J Med 2003;22:295-300.
Lara González AL, Martínez Jaimes A, Romero Arauz JF. Microalbuminuria: Early prognostic factor of preeclampsia? Ginecol Obstet Mex 2003;71:82-6.
Bar J, Hod M, Erman A, Friedman S, Gelerenter I, Kaplan B, et al.
Microalbuminuria as an early predictor of hypertensive complications in pregnant women at high risk. Am J Kidney Dis 1996;28:220-5.
Poon LC, Kametas N, Bonino S, Vercellotti E, Nicolaides KH. Urine albumin concentration and albumin-to-creatinine ratio at 11(+0) to 13(+6) weeks in the prediction of pre-eclampsia. BJOG 2008;115:866-73.
Singh H, Samal S, Mahapatro A, Ghose S. Comparison of obstetric outcome in pregnant women with and without microalbuminuria. J Nat Sci Biol Med 2015;6:120-4.
Baweja S, Kent A, Masterson R, Roberts S, McMahon LP. Prediction of preeclampsia in early pregnancy by estimating the spot urinary albumin:creatinine ratio using high performance liquid chromatology. BJOG 2011;118:1126.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]