Comparison of serum calcium and magnesium between pre-eclampsia and normotensive pregnant women:a prospective stud

Background: A large percentage of maternal mortality is related to hypertensive disorders of pregnancy. The etiology of preeclampsia is uncertain with imbalance between vasoconstrictor and vasodilators leading to vasospasm and endothelial dysfunction. Magnesium and Calcium plays a role in vascular smooth muscle contraction and thus regulating blood pressure. Aim: We compared the serum level of Calcium and Magnesium of preeclamptic women with normotensive women at SRMS-IMS, Bareilly. Method: 30 preeclamptic patient between 18-35 years with BP>140/90mmHg and gestation age >30 weeks were selected. Blood sample were taken for serum calcium and magnesium level and the results were compared with 20 normotensives pregnant. Result: Mean serum Calcium and Magnesium level in preeclamptic woman was 9.00± 0.47 and 1.90±0.31 mg/dl, respectively. Mean serum Calcium and Magnesium in normal pregnant woman was 9.12±0.37 and 1.92±0.23mg/dl, respectively. There was statistically no significant difference with p value of 0.34 and 1.00, respectively. Conclusion: Serum Calcium and Magnesiumlevelwere observed to be same in preeclamptic and normotensive pregnant women.


Introduction
Pregnancy is principally a phenomenon of maternal adaptation to increasing demands of growing fetus associated with progressive anatomical and physiological changes in all body system along with biochemical adaptation. Delivery of substance essential for fetal and placental growth, metabolism and waste removal is dependent on adequate perfusion of placental intervillous space brought by vascular refractoriness to pressure agents [1]. Preeclampsia is a pregnancy specific syndrome that can affect virtually every organ system [2]. Its incidence in India is 8-10%. Hypertensive disorder including eclampsia accounts for 13-16% maternal mortality worldwide and 5% in India [3,4]. Etiology of preeclampsia is multifactorial associated with maternal maladaptation to cardiovascular or inflammatory changes along with abnormal trophoblastic invasion of uterine vessels or immunological maladaptation or related to genetic factor leading to intense vasospasm and endothelial cell injury [2]. During normal pregnancy there is a change in level of electrolytes and mineral requirement, there is a decline in total serum calcium which follows reduction in plasma albumin concentration and also serum magnesium level declines [1]. Fluctuation in maternal serum ions maybe precipitating cause of elevated blood pressure in preeclampsia [5]. A study conducted by Dwivedi et al showed a reduced level of serum calcium and magnesium among women with preeclampsia in third trimester [6].
Dietary deficiency of magnesium has been established to play a role in blood pressure regulation and hence development of preeclampsia while Villar and co-workers showed that calcium supplementation is effective in decreasing perinatal mortality [7,8].
Golmohammed et al found no difference in calcium and magnesium level in preeclamptic women compared to normotensive [9].
Thus role of serum calcium and magnesium in patient with preeclampsia remains uncertain.We therefore sought to compare serum calcium and magnesium level in preeclamptic and normal pregnant women.

Original Research Article
Obsgyne Review: Journal of Obstetrics and Gynecology Available online at: www.medresearch.in 30 | P a g e

Materials and Methods
Place of study: Study was conducted in Obstetrics and Gynaecology department of rural tertiary care hospital in SRMS-IMS, Bareilly.
Sample size: Fifty (50) patients admitted with term pregnancy were included in study. Thirty (30) with raised blood pressure were enrolled under our study as cases and rest twenty (20) patients with normal blood pressure were termed as control.
Study design: Randomized controlled trial.
Inclusion criteria: All patients with term gestation with singleton pregnancy.
Exclusion criteria: Following conditions which are likely to aggravatepre-eclampsiawere excluded for example: a) Multiple pregnancies b) Pregnancy with confounding risk factors like chronic hypertension, renal pathology. c) Diabetes, anaemia or Rh isoimmunised pregnancy.
Sample collection: Data was obtained in a structured data sheet with variables of age, gestation age, parity, systolic and diastolic blood pressure, mean arterial pressure and BMI.4ml of venous blood sample was obtained in plain vial and sent to laboratory for analysis. Sample was centrifuged and serum calcium was measured by Arsenazo III method while serum magnesium was measured by Xylidyl blue method.

Results
In our study, majority of women were in age group of 21-25 years with period of gestation between 37-41 weeks

G= Gravida
Maximum patient of preeclampsia were nullipara Mean serum calcium in preeclamptic patient was 9.00±0.47 mg/dl and 9.12±0.37 mg/dl in normotensive patient which was statistically not significant. No significant change in serum calcium was also observed between mild and severe preeclampsia with a p value of 0.31.
Similarly serum magnesium level in normotensive women was 1.92±0.23mg/dl against 1.90±0.31mg/dl in preeclamptic which was also not significant statistically, even when compared between mild and severe preeclampsia.
Even the ratio of calcium: magnesium had no significant change between mild and severe preeclampsia or between preeclamptic and normotensive women.

Discussion
Preeclampsia occurs in 8-10% of pregnancies inIndia. Nulliparity is the most common feature of women who develops preeclampsia as most first pregnancy occurs in young women and most cases of preeclampsia or eclampsia occurs in this age group because of limited sperm exposure as concluded in study by Einarsson et al [10] and Sadat Z et al [11].
Obesity is a risk factor for preclampsia, the incidence of preeclampsia increases with maternal BMI [12]. Even in women with normal weight, there is a linear relationship between prepregnant BMI and frequency of preeclampsia [13]. In our study the mean BMI of preeclamptic patient was 27.17±4.58 and normotensive women was 24.44±3.63 which was statistically significant (p value 0.03) and the finding was consistent with the study conducted by Kanagal et al [14] and Akhtar et al [15].
Serum calcium and magnesium are important cofactor for various enzymatic processesand water balance in cells [16]. These trace element plays an essential role in vascular smooth muscle tone and contraction, and hence are vital in blood pressure regulation [17]. Calcium and magnesium both act on smooth muscle and regulates blood pressure. Variety of calcium binding sites (eg. Troponin, parvalbumin, myosin and calmodulin) that plays a role in regulation of muscle contraction. Major effect of magnesium is to reduce the rate of calcium binding sites that bind magnesium and calcium competitively [18]. Lowering of serum calcium and increase of cellular calcium led to constriction of smooth muscle in blood vessel and increase of vascular resistance [19]. Magnesium plays a role in neurochemical transmission and peripheral vasodilatation and promotes vascular muscle relaxation [19,20].Magnesium deficiency through its lack of inhibition of calcium on smooth muscle produces increased peripheral resistance [21]. Magnesium lowers blood pressure by acting like natural calcium channel blocker, competes with sodium for binding site on vascular smooth muscles cells, increases PGE, binds to potassium in a cooperative manner and induces endothelial dependent vasodilatation and blood pressure reduction [22]. Magnesium act peripherally to produce peripheral vasodilatation by increasing the prostacyclin release from endothelial cell which act as a potent vasodilator and causes fall in blood pressure. Low level of magnesium predisposes to an increase in atrial pressure by increasing the vasoconstrictor effect of angiotensin II and noradrenalin [23].
A decrease in serum magnesium level as possible etiology of preeclampsia have been reported in various studies [24,25]. However Cochrane review did not found high quality evidence on dietary magnesium supplementation for prevention of preeclampsia [26]. Low serum calcium has been implicated as a cause of preeclampsia in some studies [14,27]. Stimulation of 1,25-dihydroxy cholecalciferol has been implicated in this vasoconstrictive mechanism [27]. Reduce calcium level increases release of parathyroid hormone and rennin which in turn causes increase intracellular calcium in vascular smooth muscle and sodium retension leading to increase vascular resistance and vasoconstriction leading to rise of blood pressure [27]. Magnesium is essential for release of PTH, mild magnesium deficiency increases PTH secretion and reduction in serum calcium causes increase in release of PTH and Renin causing increase intracellular calcium in smooth muscle leading to rise in blood pressure [28,27].
This concept of reduced serum calcium in preeclampsia is not universally accepted [9,29]. Some studies have shown reduced level of 1,25-dihydroxycholecalciferol in preeclamptic compared to normal pregnant women which increases parathyroid level causing calcium reabsorption from renal tubules and intestines causing no significant change in calcium level [19,20,30]. Therefore, hypocalcemia and hypomagnesemia as etiology of preeclampsia are not an universal finding [19,20,31].
Our study showed no significant change in serum calcium level between preeclamptic and normotensive women. Similar result were observed in study conducted by Ugwuja et al [32], Golmohhamed et al [9] and Adewoluet al [33]. A study by Ebenezer et al [5] also observed no significant change in calcium level which is consistent with our study.

Original Research Article
Obsgyne Review: Journal of Obstetrics and Gynecology Available online at: www.medresearch.in 32 | P a g e No significant change in serum magnesium level was observed in preeclampsia in our study which is consistent with studies conducted by PunthumapolC [20], Adewolu et al [33], Golmohhmed et al [9] and Ebenezer et al [5].
However other studies conducted by Kanagal DV et al[14], Akhtar S et al [15] showed a low level of calcium among preeclamptic women and low magnesium level were observed in studies conducted by Indumati et al [34] and Ugwuja et al [32]. In difference to our study low level of both serum calcium and magnesium in preeclamptic women was observed in studies conducted by Jain S etal [27] and Ephraim RKD et al [35].

Conclusion
Great emphasis of dietary calcium and magnesium has been shown by different studies but our study did not show any significant variation in serum calcium and magnesium level among preeclamptic and normotensive women. Our study being a very small study, larger trials are required to establish a definite correlation. of biochemistry and lab staff for their support in providing reports.
With this I also want to thank Dr. J.K.Goel for his proof reading.We are also grateful to all those authors whose articles are cited and included in references of this manuscript.
As per available researches till now, all studies are supporting administration of calcium supplementations in antenatal period, whereas contrary to the existing data we have found that there is no such role.

Ethical issues:
The study was conducted after approval from ethical and protocol review committee of the institute.
Funding: Nil, Conflict of interest: Nil Permission from IRB: Yes