STUDY OF THYROID PROFILE, URIC ACID, CREATININE AND LIPID PROFILE IN PRE-ECLAMPSIA PATIENT

Objectives: (1) To evaluate and compare the thyroid profile and lipid profile in preeclampsia in a normotensive pregnant female in the third trimester of pregnancy. (2) To estimate and compare serum uric acid and serum creatinine in preeclampsia in normotensive pregnant females. Methods: In the present study, 154 patients, of which 79 preeclampsia (cases) and 75 (controls), were selected randomly and matched with their gestational age in patients who attended an ANC clinic at the Department of Obstetrics and Gynecology, NSCB Medical College, Jabalpur, from March 2016 to August 2017. All patients were evaluated for their lipid profile, thyroid profile, serum uric acid, and serum creatinine. The study includes patient’s specific detailed clinical history, physical examination findings, and a report of relevant investigations recorded from the patient who presented with pre-eclampsia and normotensive pregnant female attending the ANC Clinic of N.S.C.B. Medical College, Jabalpur. Results: The most common age group for preeclampsia was 20–24 years. Preeclampsia was most common in the nullipara as compared to the multipara. Pre-eclampsia cases commonly occur in low-socioeconomic and rural areas. In this study, pre-eclamptic women showed higher serum concentrations of total cholesterol (221.60±22.55), low density lipoprotein (LDL) (134.44±16.96), Very LDL (48.48±6.88) and Triglyceride (243.50±32.33) when compared to normotensive women, which was statistically significant. In this study, a statistically significant decrease in HDLC (34.55±5.37) was observed in pre-eclamptic women. An increase in serum creatinine was observed in women with pre-eclampsia. The mean serum creatinine level was (1.21±0.47). Conclusion: Our study concludes that nulliparous and low-socio-economic women had a higher risk of pre-eclampsia. Maternal age between 20 and 24 years are more prone to develop pre-eclampsia. Serum uric acid levels are significantly higher in pre-eclampsia patients and could be a useful indicator of maternal and fetal complications in hypertensive patients.


INTRODUCTION
Pre-eclampsia continues to be a major obstetric challenge in presentday of medical practice. It is one of the leading causes of maternal, fetal/neonatal morbidity and mortality worldwide. Pre-eclampsia is a multisystem disorder of pregnancy that is characterized by hypertension (blood pressure >140/90 mm Hg) and proteinuria (urinary protein excretion of >300 mg in 24 h urine) after 20 weeks of gestation in previously normotensive nonproteinuric pregnant women [1,2]. The major cause of fetal compromise in pre-eclampsia is a reduction in utero-placental perfusion [3,4]. Pre-eclampsia occurs in 7-10% of pregnancies worldwide. In India, the incidence is reported to be high, approximately 8-10% of the pregnancies [5].
In cases of nonintervention, pre-eclampsia may progress to the dreaded complications like eclampsia, HELLP syndrome, pulmonary edema, abruptio placentae, postpartum circulatory collapse, acute renal failure, hepatic rupture, cerebral hemorrhage, and visual disturbances, including death. These conditions are also major causes of neonatal morbidity and mortality [6]. Despite considerable research, the etiology of pre-eclampsia remains obscure. Many theories have been proposed to explain the pathophysiology of preeclampsia [7]. Pregnancy is a physiological process. In pregnancy, maternal physiological adjustments of the multi-organ system are seen. The adjustments are metabolic, circulatory, and hormonal [8]. The pathogenesis of pre-eclampsia appears to occur in two phases: abnormal implantation of the placenta leading to impaired placental blood flow, which in turn includes the release of pathogenic factors in the maternal circulation resulting in endothelial injury to many maternal organs, especially the kidney, and liver [9]. In pre-eclampsia the liver, kidneys, and brain are mostly affected. Due to autointoxication, functional disorders in these organs are evident [10]. This injury leads to various biochemical changes. The alteration of serum lipid profiles in pre-eclampsia is well documented. An abnormal lipid profile is known to be strongly associated with atherosclerotic cardiovascular diseases. It has a direct effect on vascular endothelial dysfunction [11]. The liver, kidneys, and muscles are the main organs of peripheral deiodination from T4 to T3. The serum concentrations of T4 and T3 may differ in pre-eclampsia from normal pregnancy [12]. There are several potential origins for uric acid in pre-eclampsia. Abnormal renal function, increased tissue breakdown, acidosis, and increased activity of the enzyme xanthine oxidase/dehydrogenase causes a rise in uric acid [13,14]. Creatinine is an anhydride of creatine. Serum creatinine concentrations depend on the balance between their production and excretion. The rise in creatinine in preeclampsia is due to increased production and a reduction in excretion [15]. The above-mention biochemical and hematological parameters affect maternal and fetal morbidity and mortality directly or indirectly. A successful pregnancy outcome requires frequent monitoring of these parameters to avoid complications throughout the pregnancy. Thus, in the present study, we evaluated the serum lipid profile, creatinine, uric acid, and thyroid hormonal concentration in pre-eclampsia women and compared them with those of normal pregnant women.

METHODS
154 patients, 79 pre-eclampsia (cases) and 75 (controls), were selected for the present study by a simple random sampling method during the

Sampling method and source of data-patients
Attending ANC clinics at the Department of Obstetrics and Gynaecology who fulfil the inclusion criteria were selected for the study by simple random sampling after obtaining written informed consent. Study variable, included demographic data, family and personal histories of pre-eclampsia, hypertension, diabetes mellitus, and investigations details were recorded in the study proforma. After consent, 5 mL of blood was drawn under aseptic precaution from the antecubital vein and collected in an EDTA and a plane tube.

OBSERVATION AND RESULTS
In this present study, a total of 154 cases were included. 79 were presented with pre-eclampsia and 75 were included as a control group with a normal pregnancy. They were analyzed and compared using different parameters. The observations are tabulated and analyzed as follows: Table 1 shows the age distribution among the PE and normal control groups. They were included in four major groups (<20, 20-24, 25-29, and 30-34). In the Mahakoushal region, a high incidence of preeclampsia was observed between 20-24 and 25-29 years of age. The mean age in pre-eclamptic patients was 24.51±3.707 years.
This Table 2 shows distribution of tri-iodothyronine (T3) in preeclampsia cases and the normal group. It is observed that (31.6%) of pre-eclampsia cases show a higher T3 value and 68.4% show a T3 value normal. The values are compared with normal cases, 52% of cases showing a higher T3 value and 48.0% of cases showing a normal T3 value. The observation suggests a normal T3 value of 68.4% and a 31.6% higher T3 in pre-eclampsiacases cases. The value in comparison to higher T3 was 52% and normal T3 was 48% in the normal control group.
This Table 3 shows the distribution of tetra-iodothyronine (T4) in preeclampsia cases and the normal group. It is observed that (38%) of cases of pre-eclampsia show a higher T4 value, and 62% show a normal T4 value normal. The values are compared with normal cases, with 30.7% of cases showing a higher T4 value and 69.3% of cases showing a normal T4 value. The T4 value evaluation is not significant at p>0.05. Table 4 indicates the distribution of thyroid profile values amongst the pre-eclampsia and control groups for evaluation with mean values. An abnormal Thyroid profile is observed in pre-eclampsia cases in comparison to the normal group. The observation is significant as having -p<0.05. Table 5 shows the distribution of serum uric acid among the preeclampsia and normal groups. High s. uric acid >6 mg/dL was observed in (92.4%) of cases, while only 7.6% of PE showed normal s. uric acid values. In normal group, 51.9% of cases showed a normal s. uric acid value, while 48.1% of cases showed a high s. uric acid value.
The observation is significant as -p<0.0001. Table 6 shows the distribution of serum creatinine among pre-eclampsia and the normal group. High serum creatinine >1.2 mg/dL was observed in (19.0%) of cases, while 81.0% of pre-eclampsia showed a normal S.      The observation is significant at -p<0.01.

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creatinine value. In the normal group, almost 100% of cases showed a normal S. creatinine value. The observation is significant as -p<0.0001. Table 7 indicates the distribution of lipid profile values amongst the pre-eclampsia and control groups for evaluation with mean values. An abnormal lipid profile is observed in pre-eclampsia cases in comparison to the normal group. The observation is significant at -p‖ <0.05.

DISCUSSION
Hypertensive disease in pregnancy is a major cause of maternal and fetal morbidity and mortality1. Pre-eclampsia adversely affects the maternal and fetal outcomes due to its wide-spread multiorgan involvement. Pre-eclampsia is a complication in approximately 7-8% of all pregnancies. In our study, we observed a correlation between lipid profile, thyroid profile, serum uric acid, and serum creatinine levels and the development of pre-eclampsia. Hence, estimation of different parameters in the early second trimester can be a cost-effective way of diagnosing pre-eclampsia well in advance, because early identification of pre-eclampsia still remains the cornerstone to preventing maternal and fetal morbidity and mortality due to hypertensive disorders. In this present study, we found Table 1 that 59.1% of patients below 24 year of age and between 25 and 29 years of age developed pre-eclampsia, respectively. This suggests younger patients have a high the incidence of pre-eclampsia. It is of great significance as p<0.0001. Sheraz et al. [16] also observed and reported the same finding and stated that PE is more frequent in patients younger than 21 years of age and those older than 35 years. A similar observation was also reported by Duckitt et al. [17]. Who found teenage pregnancy to be one of the risk factors for PIH and eclampsia. In this study, pre-eclamptic women showed higher serum concentrations of total cholesterol, low density lipoprotein (LDL), Very LDL and Triglyceride (TG) when compared to normotensive women, which was statistically significant. In this study, a statistically significant decrease in HDLC was observed in pre-eclamptic women. Estrogen is responsible for the induction of TG and HDL. Estrogen levels fall in pre-eclampsia. The low level of HDL is, however, not only because of hypoestrogenemia but also due to insulin resistance [18]. The present study also showed a significant rise in TG in pre-eclamptic patients in comparison to normotensive pregnant women. The other studies that support our study are Vani et al. [19], Somani et al. [20], and Gohil et al. [21].
Uric acid, an end product of purine catabolism catalyzed by xanthine oxidase, is filtered, reabsorbed, and secreted by the kidney. In preeclampsia, glomerular endothelial lesions lead to diminished renal blood flow and glomerular filtration rate, as well as impaired tubular reabsorption. Hyperuricemia in pre-eclampsia is thus primarily due to decreased renal clearance and increased tubular reabsorption because of the reduction in glomerular filtration rate [24]. On the other hand, an elevated level of uric acid reflects increased uric acid production. In pre-eclampsia due to placental hypoxia, the degree of placental cell destruction increases, which is one of the rich sources of purine for the production of uric acid by xanthine oxidase [25]. This could also explain the increased uric acid concentration. Increases serum creatinine is observed in women with pre-eclampsia. These differences were significant compared with noromotensive pregnant women because pre-eclampsia is associated with a reduction in plasma renin activity and plasma renin concentration if compared with normal pregnancy [26], while the circulating level of angiotensin II may be normal during pre-eclampsia [27]. Other studies found that reducing uteroplacental perfusion pressure could increase renal sensitivity to angiotensin II through a reduction in NO or prostacyclin synthesis or by enhanced formation of TXA2 and endothelin [28].

CONCLUSION
Nulliparous and low-socio-economic women had a higher risk of preeclampsia. Maternal age between 20 and 24 years makes them more likely to develop pre-eclampsia. Serum uric acid levels are significantly higher in pre-eclampsia patients and could be a useful indicator of maternal and fetal complications in hypertensive patients. There is a strong correlation between dyslipidemia and the development of preeclampsia. Hence, estimation of the lipid profile in the early second trimester can be a cost-effective way of diagnosing pre-eclampsia well in advance because early identification of pre-eclampsia still remains the cornerstone to preventing maternal and fetal morbidity and mortality due to hypertensive disorders. Hence, we conclude that maternal dyslipidemia in pregnancy is a very good predictor of preeclampsia. Pre-eclamptic patients had significantly higher levels of TSH and low levels of T3 and T4 in comparison to normotensive pregnant women. However, the changes in thyroid hormones did not correlate with the severity of pre-eclampsia. Urinary micro albuminuria should be considered an important indicator for pre-eclampsia, so it can be used as a screening test.

ACKNOWLEDGMENT
We are thankful to the whole Pathology and OBGY department, NSCB, Jabalpur; without their support, this study would not have been possible.

AUTHORS CONTRIBUTIONS
CD: Concept and design of the study; aims and objectives; reviewed the literature; prepared the first draft of the manuscript; arranged all the references; and this is his own dissertation work; RU Contributed regarding the conception or design of the study, developing the consent form, data collection, interpreting the results, and manuscript preparation; DD: Concept, coordination, statistical analysis and In the present study, we also found an increased serum uric acid level in pre-eclamptic women, which was statistically significant. Our result is in agreement with other studies (Sayyed and Sontakke, Sunita et al., Sirajwala et al., Bainbridge and Roberts). Elevated serum uric acid often precedes clinical manifestations of the disease. Bainbridge and Roberts observed hyperuricemia in 75% of women with clinically diagnosed pre-eclampsia [23].

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interpretation, preparation of the manuscript, and revision of the manuscript.