To Assess the Association of Maternal Serum Uric Acid and C- Reactive Protein with Severity of Pre-Eclampsia In A Tertiary Care Hospital, Rajasthan, India

INTRODUCTION:

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality, especially in low- and middle-income countries [1]. Characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, it is a multisystem disorder that may progress to eclampsia and serious maternal-fetal complications [2]. Despite extensive research, its exact pathophysiology remains unclear, and reliable tools for early prediction and severity assessment are lacking [3]. Biochemical markers like serum uric acid and C-reactive protein (CRP) have gained interest for their potential role in assessing disease severity [4]. Uric acid, traditionally seen as a marker of renal dysfunction, is now recognized for its pro-inflammatory, oxidative, and vasoconstrictive properties, contributing to disease progression and complications such as IUGR and placental abruption [5,6]. Its levels rise abnormally early in pre-eclampsia, possibly due to impaired renal excretion or oxidative stress [7]. Similarly, CRP, an acute-phase protein elevated in response to systemic inflammation, has been found to be significantly raised in pre-eclamptic pregnancies [8]. It reflects the exaggerated maternal immune response to placental ischemia and may correlate with disease severity [9]. Inflammatory mechanisms are now understood to play a central role in pre-eclampsia pathogenesis, alongside vascular and renal dysfunction [10].A combined evaluation of uric acid and CRP may offer better insights into both metabolic and inflammatory components of the disease [11]. As affordable and widely available tests, they are especially useful in low-resource settings like India [12]. Hence, this study aims to investigate the association of maternal serum uric acid and CRP levels with the severity of pre-eclampsia in a tertiary care setting.

AIMS:

This study aimed to evaluate whether there is a significant difference in serum uric acid and C-reactive protein (CRP) levels between women with pre-eclampsia and normotensive pregnant women, and to assess the potential of these biomarkers in predicting the severity of pre-eclampsia.

METHODS:

This was a hospital-based, observational study conducted in the Department of Obstetrics and Gynaecology at Sardar Patel Medical College and Associated Group of Hospitals, Bikaner, Rajasthan—a tertiary care center catering to a large population in the northwestern region of India.The study was carried out over a period of six months following approval from the Institutional Ethics Committee.A total of 252 pregnant women attending the antenatal clinic (ANC), obstetrics wards, or labour room were enrolled and divided into two groups:Group A (Cases): 126 women diagnosed with pre-eclampsia or eclampsia & Group B (Controls): 126 normotensive pregnant women without any known medical complications .Participants were selected from inpatient and outpatient services based on clinical criteria and relevant investigations. Inclusion Criteria for the case included were: Pregnant women aged 18–40 years with Gestation age ≥ 32 weeks having Singleton live pregnancy, diagnosed with pre-eclampsia or eclampsia (for Group A) And who were Willing to participate and provide informed written consent. None of the patients included were in active labour or had diabetes mellitus, cardiovascular disease, endocrine disorders, Essential hypertension, Seizure disorder, Severe anemia, conditions known to affect serum uric acid or CRP levels, including:Metabolic syndrome or liver disorders, Acute or chronic kidney disease, Gouty arthritis,Multifetal pregnancies or known fetal anomalies. The normal range of parameter taken for these biomarkers are as follows:

URIC ACID (serum) – Normal levels:

Units

Nonpregnant adult

First trimester

Second

trimester

Third

trimester

mg/dL

2.5-5.6

2.0-4.2

2.4-4.9

3.1-6

Normal CRP levels, with mean of 0.81 mg/l at 5–7 weeks of gestation, 2.85 mg/l at 19–20 weeks of gestation, and 3.89 mg/l at 32 weeks of gestation22. Elevated CRP is defined as higher than 5 mg/l. (Dati et al., 1996).

RESULTS& DISCUSSION:

In the present study, the mean age was 25.67 ± 4.08 years in normotensive women and 25.64 ± 4.90 years in preeclamptic women, showing no significant difference. This is comparable to the findings by Tesfa et al [13]., who also reported a similar mean age of 27.33 ± 4.45 years in normotensive women and 27.98 ± 5.64years in the preeclampsia group.38 On the other hand, Mosayebi et al [14]. observed a slightly higher mean age ( 27.79 ± 4.43 years) in preeclampsia than normotensive pregnant women ( 26.19 4.44 years), suggesting regional or lifestyle differences might influence the age at which pregnancy complications manifest.

Table 1: Distribution of the cases according to age groups

Age Group (Years)	Group A Normotensive		Group B Preeclampsia
Age Group (Years)	No.	%	No.	%
≤19	7	5.56	12	9.52
20-24	46	36.51	44	34.92
25-29	52	41.27	46	36.51
30-35	17	13.49	18	14.29
>35	4	3.17	6	4.76
Total	126	100.00	126	100.00
Mean ± SD	25.67 ±4.08		25.64 ±4.90
p value	7.707

Systolic and diastolic pressures were significantly elevated in the preeclampsia group (158.92 ± 12.09 mmHg systolic, 94.19 ± 7.40 mmHg diastolic) compared to normotensive women (118.64 ± 6.92 mmHg systolic, 78.42 ± 6.69 mmHg diastolic, p = 0.0001). These results correspond with the findings of Kameshwarama et al.[15], & Tesfa et al.[13] where mean blood pressure in case group is 165.25±26.5/ 103.25±14.52, 155.30±10.85/99.38±7.7 resp. which is much higher than in control group i.e., 119.25±10.24/77.6±7.27, 110.75±8.49/71.25±7.53,p>0.001 indicating a strong correlation between hypertension and biochemical inflammatory markers in preeclampsia.

Table 2: Distribution of the cases according to Systolic Blood pressure

Systolic Blood pressure (mmhg)	Group A Normotensive		Group B Preeclampsia
	no.	%	no.	%
< 130	111	88.10	0	0.00
130-160	15	11.90	100	79.37
>160	0	0.00	26	20.63
Total	126	100.00	126	100.00
Mean SD	118.64 6.92		158.92 12.09
p value	0.0001

Table no. 3: Distribution of the cases according to diastolic Blood pressure

Diastolic Blood pressure (mmhg)	Group A Normotensive		Group B Preeclampsia
	no.	%	no.	%
<80	61	48.41	0	0.00
80-100	65	51.59	112	88.89
>100	0	0.00	14	11.11
Total	126	100.00	126	100.00
Mean SD	78.42± 6.69		94.19± 7.40
p value	0.0001

Table 04: Distribution of cases according to level of proteinuria

Proteinuria Level	*Group A Normotensive*		*Group B Preeclampsia*
	No.	%	No.	%
No Proteinuria	118	93.65	24	19.05
+1 Proteinuria	6	4.76	46	36.51
+2 Proteinuria	2	1.59	32	25.40
+3 or more Proteinuria	0	0.00	24	19.05
Total	126	100.00	126	100.00
p value	0.0001

Proteinuria was significantly higher among preeclamptic women in our study: 81% showed +1 or more proteinuria, compared to 6.35% in the normotensive group (p = 0.0001). These findings were similar to that of Kushwaha et al.[16], where maximum number of cases with preeclampsia had +3 proteinuria (55%) and in control group 58% of patients had +1 proteinuria. Similarly, Kameshwaramma et.al[15], in study group A (cases), maximum number of patients had severe proteinuria (+3) i.e. 55%, and in group B(controls), maximum number of patients had proteinuria of +1, i.e., 55.7% (p=0.001), which emphasized proteinuria as a hallmark of preeclampsia and correlated it with disease severity and renal involvement.

The mean uric acid levels were significantly higher in preeclamptic women (6.20 ± 2.29 mg/dL) versus normotensive group (4.79 ± 1.65 mg/dL, p= 0.0001). Comparable findings were reported by Mandal et al. [17] (5.46±1.84 mg/dL in cases vs. 3.65±1.09 mg/dL in control) and Singh et al.[18] (6.26±1.31 mg/dL in cases vs. 3.99±0.89 mg/dL in controls). Similar observations were drawn by Kaur P et al. [19], where the mean uric acid levels in cases was 5.8±1.8 mg/dL which is quite higher than that of control group, i.e., 4.1±1.05 mg/dL, where the difference is statistically significant(p=0.0001), reinforcing the use of uric acid as a potential predictive biomarker for severity of preeclampsia

Table no. 05 Distribution of cases according to Uric Acid level

Uric Acid (mg/dL)	Group A Normotensive		Group B Preeclampsia
	No.	%	No.	%
< 2.4	5	3.97	3	2.38
2.4-5.7	89	70.63	58	46.03
>5.7	32	25.39	65	51.59
Total	126	100.0	126	100.0
Mean ± SD	4.79±1.65		6.20±2.29
p value	0.0001

Although our study showed slightly elevated CRP levels in preeclamptic women (19.66 ± 18.60 mg/L) than normotensive women (17.91 ± 16.94 mg/L), the difference was not statistically significant(p = 0.436). These findings were similar to Mandal et al.[17] and Kushwaha et al.[16], where mean CRP levels in cases were 8.14±6.3 mg/L and 8.26±6.9 mg/L and in controls were 6.28±4.66 mg/L and 6.22±4.29 mg/L respectively, which showed non-significant differences. However, Kaur P et al.[19] observed a statistically significant elevation (6.8 ± 3.4 mg/L in cases v/s 5.4 ± 2.8 mg/L in controls) (p = 0.02), suggesting the variability in CRP’s predictive reliability across different populations and gestational timings.

Table no. 06: Distribution of cases according to CRP level

CRP	Group A Normotensive		Group B Preeclampsia
	No.	%	No.	%
<6	36	28.57	28	22.22
≥ 6	90	71.43	98	77.78
Total	126	100.00	126	100.00
Mean SD	17.91±16.94		19.66±18.60
p value	0.436

Table no. 07: Association of Uric Acid and CRP levels

Uric Acid	Group A Normotensive				Group B Preeclampsia				P value
	CRP <6		CRP ≥6		CRP <6		CRP ≥6
	No.	%	No.	%	No.	%	No.	%
< 2.4	2	5.56	3	3.37	1	3.57	3	2.04	0.003*
2.4-5.7	26	72.22	63	70.79	13	46.43	45	45.92
>5.7	8	22.22	23	25.84	14	50.00	51	52.04
Total	36	100.00	89	100.00	28	100.00	99	100.00

In Group A (Normotensive), maximum, 23 cases (74.19%) were in >5.7mg/dL uric acid level whereas in group B (Preeclampsia), maximum, 51 cases (78.46%) in >5.7mg/dL uric acid level. The association between Uric acid and CRP is found to be statistically significant in both groups (p=0.003). Similarly, Suliman et al .[20] revealed significantly elevated levels of CRP and UA in both mild (15.17±0.78 mg/L and 6.44±0.293 mg/dL) and severe (31.5±1.709 mg/L and 7.37±0.27 mg/dL) preeclamptic groups compared to controls (4.79±0.178 mg/L and 4.0±0.061 mg/dL) respectively (p < 0.001). CRP and UA also increased with severity and positively correlated with mean arterial pressure (r > 0.7; p < 0.001). Also, Rekha etal. [21] found that elevated CRP and uric acid levels are closely associated with the severity and progression of preeclampsia and may aid in its early detection and management.

CONCLUSION:

Preeclampsia is a complex multifactorial disease. Our study set the importance of biochemical markers like serum uric acid and CRP. Uric acid showed a statistically significant elevation in preeclamptic women while CRP levels were elevated, but nonsignificant. Proteinuria remained a robust clinical marker for disease presence and severity. Our study suggest the incorporation of uric acid testing in routine prenatal screening protocols, especially in primigravida women presenting with borderline hypertension or proteinuria. This study was conducted with the aim of promptly identifying and managing patients of preeclampsia. Enhanced antenatal surveillance, particularly in booked urban women, may aid in timely diagnosis and intervention, thereby improving maternal and neonatal outcomes

REFERENCES:

1. Duley L. The global impact of pre-eclampsia and eclampsia. InSeminars in perinatology 2009 Jun 1 (Vol. 33, No. 3, pp. 130-137). WB Saunders.

2. Dimitriadis E, Rolnik DL, Zhou W, Estrada-Gutierrez G, Koga K, Francisco RP, Whitehead C, Hyett J, da Silva Costa F, Nicolaides K, Menkhorst E. Pre-eclampsia. Nature reviews Disease primers. 2023 Feb 16;9(1):8.

3. Chappell LC, Cluver CA, Tong S. Pre-eclampsia. The Lancet. 2021 Jul 24;398(10297):341-54.

4. Martin AC, Brown MA. Could uric acid have a pathogenic role in pre-eclampsia?. Nature reviews nephrology. 2010 Dec;6(12):744-8.

5. Thangaratinam S, Ismail KM, Sharp S, Coomarasamy A, Khan KS. Accuracy of serum uric acid in predicting complications of pre‐eclampsia: a systematic review. BJOG: An International Journal of Obstetrics & Gynaecology. 2006 Apr;113(4):369-78.

6. Prakash S, Sharma N, Kumari P, Kumar A. Serum uric acid as marker for diagnosing preeclampsia. International Journal of Pharmaceutical Sciences and Research. 2012 Aug 1;3(8):2669.

7. Gupta R. Study of Serum Uric Acid as a Predictor of Severity of Pre-Eclampsia and Perinatal Outcome at RRMCH (Master's thesis, Rajiv Gandhi University of Health Sciences (India)).

8. Hamadeh R, Mohsen A, Kobeissy F, Karouni A, Akoum H. C-reactive protein for prediction or early detection of pre-eclampsia: a systematic review. Gynecologic and obstetric investigation. 2021 Apr 26;86(1-2):13-26.

9. Uckan K, Sahin HG. Serum amyloid A, procalcitonin, highly sensitive C reactive protein and tumor necrosis factor alpha levels and acute inflammatory response in patients with hemolysis, elevated liver enzymes, low platelet count (HELLP) and eclampsia. Journal of Obstetrics and Gynaecology Research. 2018 Mar;44(3):440-7.

10. Verma A. Evaluation of the Diagnostic Value of the Early Second-Trimester Maternal Serum High Sensitivity C-Reactive Protein Level for Prediction of Pre-Eclampsia–A Prospective Study (Master's thesis, Rajiv Gandhi University of Health Sciences (India)).

11. Kucukgoz Gulec U, Tuncay Ozgunen F, Baris Guzel A, Buyukkurt S, Seydaoglu G, Ferhat Urunsak I, Cuneyt Evruke I. An analysis of C‐reactive protein, procalcitonin, and D‐dimer in pre‐eclamptic patients. American journal of reproductive immunology. 2012 Oct;68(4):331-7.

12. Onuegbu AJ, Olisekodiaka JM, Udo JU, Umeononihu O, Amah UK, Okwara JE, Atuegbu C. Evaluation of high-sensitivity C-reactive protein and serum lipid profile in southeastern Nigerian women with pre-eclampsia. Medical Principles and Practice. 2015 Apr 21;24(3):276-9.

13. Tesfa E, Munshea A, Nibret E, Mekonnen D, Sinishaw MA, Gizaw ST. Maternal serum uric acid, creatinine and blood urea levels in the prediction of pre-eclampsia among pregnant women attending ANC and delivery services at Bahir Dar city public hospitals, northwest Ethiopia: A case-control study. Heliyon. 2022 Oct 1;8(10).

14. Mosayebi G. Association of Uric Acid and C-Reactive Protein with Severity of Preeclampsia in Iranian VVomen" A. Ghazavi," G. Mosayebi," E. Mashhadi. J. Med. Sci. 2008 Apr 1;8(3):239-43.

15. Kameswaramma K. Association of C-reactive protein and uric acid with severity of preeclampsia attending to teaching hospital.

16. Kushwaha et al.(2023) An Analytical Comparative Assessment of the Association of CRP and Uric Acid with Severity of Preeclampsia. International Journal of Current Pharmaceutical Review and Research 2023; 15(4); 51-56

17. Mandal KK, Singh YP, Das A, Devi NS, Singh NN, Singh WG. Serum uric acid and C-reactive protein in preeclampsia. IOSR J Dent Med Sci. 2015;14(2):16-23

18. Singh D, Rahman A, Kanti V. A comparison of serum levels of uric acid, c-reactive protein and nitric oxide in preeclampsia patients and normal healthy pregnant females. International Journal of Clinical Biochemistry and Research. 2023 Apr 14;10(1):77-80.

19. Kaur P, Desai DA, Taraiya A, Patel A. Association of serum uric acid and C-reactive protein levels in prediction of pre-eclampsia. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2016 Feb 1;5(2):495-503

20. Suliman NA, Awadalla KE, Bakheit KH, Mohamed AO. Cancer antigen 125 and C-reactive protein inflammatory mediators and uric acid in association with preeclampsia in North Kordofan State, Western Sudan. PLoS One. 2023 Jan 23;18(1):e0280256

21. Dr. K. Rekha, Dr. P. Mohan Kumaresh 2019 Putative Role of Serum Uric Acid and hsCRP in Preeclampsia Scholar journals of applied medical science

To Assess the Association of Maternal Serum Uric Acid and C- Reactive Protein with Severity of Pre-Eclampsia In A Tertiary Care Hospital, Rajasthan, India

Article Information:

Abstract:

Keywords:

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INTRODUCTION:

METHODS:

RESULTS& DISCUSSION:

CONCLUSION:

REFERENCES:

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