August 1991, Volume 41, Issue 8

Original Article

SERUM CALCIUM, UREA AND URIC ACID LEVELS IN PRE-ECIAMPSIA

Talat J. Hassan  ( PMRC Research Centre and Jinnah Postgraduate Medical Centre, Karachi. )
Agha Sadaruddin  ( PMRC Research Centre and Jinnah Postgraduate Medical Centre, Karachi. )
Sadiqua N. Jafarey  ( Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi. )

ABSTRACT

Serum calcium, urea and uric acid levels were determined in 100 normal pregnant women and 50 patients with pre-eclampsia. Serum calcium levels were significantly lower and urea and uric acid levels higher in pre-eclampsia. Low levels of calcium were found as early as 28 weeks and can therefore be used for early diagnosis of pre-eclampsia. (JPMA41: 183, 1991).

INTRODUCTION

Pre-eclampsia is a common obstetric disorder characterised by hypertension and proteinuria. It is associated with a higher foetal risk than non-proteinuric hypertension of pregnancy. Mild, or even barely recog. nisable pre-eclampsia may progress to eclampsia which is potentially lethal for both the mother and foetus1. Its incidence is gradually declining in the West with effective efforts2. Although no single clinical feature of pre­eclampsia is pathognomonic for the disease, some studies have shown a correlation between certain biochemical parameters and pre-eclampsia3-5. These include altered blood levels of calcium, urea and uric acid. This case control study was designed to establish whether such a relationship existed between these parameters and pre-eclampsia among our subjects.

PATIENTS AND METHODS

Fifty patients with pre-eclampsia and 100 normal pregnancy women attending antenatal clinic were studied. To exclude cases with mistaken diagnosis, the stringent criteria used for selection of cases were, nulliparity, proteinuria, reliable history of cardiovascular and renal normality or better follow-up studies proving it, normal fundoscopic findings to exclude long standing hypertension, age less than 35 years, no history of cortisone or hormone therapy and an acute rise of blood (>20mm of Hg) above the previously existing diastolic pressure or a blood pressure of >140/90 mm of Hg at or after 20 weeks of pregnancy.
Controls were matched for age, parity and gesta­tional age. Gestational age was calculated by dates (from last normal menstrual period) and ultrasound measure­ments in first half of pregnancy. Following criteria were adopted for the selection of controls. Blood pressure always <140/90mm of Hg or arise, if any, always <20mm Hg above the previously existing diastolic pressure, no proteinuria, no asymptomatic bacteriuria, no associate disease and no complication of pregnancy.
All subjects included in the study were recorded on a specially designed proforma, which included detailed history, complete physical examination including pos­tural change in blood pressure. Midstream urine was checked for proteinuria and bacteriuna to ensure ab­sence of infection. Women with asymptomatic bacteria were excluded from the study. Blood was collected by clean veinepuncture for biochemical tests. Estimation of blood, calcium urea, uric acid and creatinine was done by kit-method. Serum calcium was estimated using methyl blue, and 8-hydroxy quinoline6. Serum creatinine estima­tion was done to establish normality of renal function.
Statistical methodology
Postural change in diastolic blood pressure of >20 mm at Hg among subjects was tested by Odd’s ratio7.

RESULTS

Mean age of subjects was 22 years (range 18-28); gestational age 36 weeks (range 28-40) and 19 cases (38%) were 28-34 weeks of pregnancy. Body weight of cases (61 kg) was significantly higher as compared to that of controls (58 kg) (Table I).


Supine pressure response (rollover test) was posi­five in cases with a change in diastolic blood pressure ranging from 10-38mm Hg (Table II).


Serum values of calcium, urea, uric acid and creatmine are given in Table III.

Serum calcium was comparatively lower and urea and uric acid significantly higher in cases. Serum creatinine was within normal limits in subjects showing normality of the kidney function.

DISCUSSION

Recently much attention has been paid to relation­ship between serum calcium and blood pressure by various workers8-10. A casual relationship between serum calcium deficits and edema, proteinuria and hyperten­sion gestosis and also beneficial effect of calcium supplementation on blood pressure has been reported in pregnant women4,12. Hypocalciuria distinguishes pre­eclampsia from normal pregnancy and other forms of more benign gestational hypertension13. The hypothesis of serum calcium and blood pressure relationship during pregnancy is corroborated by our findings of low serum, calcium in cases of pre-eclampsia (Table III). The exact mechanism involved in inverse relationship between serum calcium and blood pressure is not clearly under­stood. Probably the effect of calcium is interconnected with the effect of sodium. The natriuretic hormone influences membrane permeability and leads to an increase in intracellular sodium. It also inhibits sodium -calcium exchange and causes accumulation of calcium in vascular smooth muscle cells. The increase in intracel­lular calcium would lead to an increased contractility and vascular tone resulting in an augmented peripheral vascular resistance and consequently in raised blood pressure3. Recently parathyroid (PTH) hormone is believed to be involved in this relationship. Increase in PTH in serum would lead to an increase of free intracellular calcium which in vascular smooth muscles affects the tension and triggers muscular contraction resulting in increased blood pressure12,14. Blood urea and uric acid were significantly higher among our cases as compared to controls (Table III). These findings are similar to those reported for European women’. Top­pozado15 describes raised blood urea during pregnancy as a known feature of pre-eclampsia.
Rollover test, a predictor of pre-eclampsia, was positive in our cases but not in controls. Well controlled fellowship studies may prove this test to be an important predictor of pre-eclampsia among our subjects also.
From biochemical difference among our cases of pre-eclampsia and controls an important query arises; “Will calcium supplementation during pregnancy prevent the onset of pre-eclampsia?” Some workers12-18 have demonstrated, by a series of randomized clinical trials, a reduction in blood pressure with calcium supplementation in animals, in healthy and mildly hyper­tensive subjects, and in pregnantwomen.

ACKNOWLEDGEMENT

The authors wish to acknowledge the statistical evaluation performed by Mr. S. Ejaz Alam, statistician, PMRC Research Centre, Karachi.

REFERENCES

1. Dieckmann, W.J. The toxemias of pregnancy. 2nd ed. St. Louis, Mosby, 1952, P.420.
2. Chesley, LC. Diagnosis of preeclampsia (editorial). Obstet. Gynecol., 1985; 65:423.
3. Kesteloot, H. and Geboers, J. Calcium and blood pressure. Lancet, 1982: 1:813.
4. Belizan, 3M, and Villar, J. The relationship between calcium intake and edema proteinuria and hypertension - gestosis; an hypothesis. Am. J. Clin. Nutr., 1980; 33:2202.
5. Egwuata, V.E. Plasma urate, urea and creatinine levels during pregnancy and after the puerperium in normal primigravid Nigerians. Br. 3. Obstet. Gynaecol., 1983; 90:21.
6. Barnetl, R.N. and Goldberg, M.H. Determination of Kits” used for clinical chemical analysis of calcium in serum. Am. .1. Clin. Pathol., 1973; 59;.836.
7. Morton, F.R. and Hebel, JR. Astudy guide to epidemiology and biostatistics. Baltimore. University Park Press, 1983, p.33.
8. Blaustein, M.P. Sodium ions, calcium ions, blood pressure regulation and hypertension; a reassessment. and a hypothesis. Am. .1. Physiol., 1977; 232 C: 165.
9. Sowers, M.R.,Wallace, RB. and Lemke, J.H. Theassociation of intakes of vitamin D and calcium with blood pressure amongwomen. Am. J. Clin. Nutr., 1985; 43:135.
10. McCarron, D.A. Low serum concentrations of ionized calcium in patients with hypertension. N. Engi. 3. Med., 1982; 307:226.
11. Belizan, 3M., Villar, 3., Zalazar, A., Rojaz, Z., Chan, D. and Bryce, G.F. Preliminary evidence of the effectof calcium supplementation on blood pressure in normal pregnant woman. Am. J. Obstet. Gynecol., 1983; 146:175.
12. Belizan, 3M., Villar, 3., Repke, .1. The relationship between calcium inake and pregnancy-induced hypertension. Up-to-date evidence. Am. 3. Obstet. Gynecol., 1988; 158:898.
83. Taufield, PA., Ales, K.L, Resnick, LM., Druzin, ML, Gertner. J.M. and Laragh, J.H. Hypocalciuria in preeclampsia. Ni. EngI. 3. Med., 1987; 316:715.
14. Redman. C.W. and Jefferies, M. Revised definition of pre- eclampsia. Lancer, 1988; 1:809.
15. Toppozada, M., Choneim,A., Habib, Y.A., El.Ziadi, L. and El- Damaraswy. H. Et’fectof prostaglandin Aon renal hemodynamics in pregnancy toxemia. Am. J. Obstet. Gynecol., 1979; 135:581.
16. Gant, N.F., Chand, S., Worley, R.J., Whalley, P.J., Grosby, U.D. and MacDonald, P.C. A clinical test useful for predicting the development of acute hypertension in pregnancy. Am.J. Obstet. Gynecol., 1974; 120:1.
17. Chesley, LC. and Sibai, B. Clinical significance of elevated mean arterial pressure in the second trimester. Am. 3. ObsteL Gynecol., 1988; 159:275.
18. Johnson, N.E., Smith, E.L and Freudenheim, i.L Effect on blood pressure of calcium supplementation of women. Am. i. Clin. Nurr., 1985; 42:12.

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