Journal name: Integrated Blood Pressure Control Article Designation: ORIGINAL RESEARCH Year: 2017 Volume: 10 Integrated Blood Pressure Control Dovepress Running head verso: Owusu Darkwa et al Running head recto: Serum magnesium and calcium in preeclampsia open access to scientific and medical research DOI: http://dx.doi.org/10.2147/IBPC.S129106 Open Access Full Text Article O R I G I N A L R E S E A R C H Serum magnesium and calcium in preeclampsia: a comparative study at the Korle-Bu Teaching Hospital, Ghana Ebenezer Owusu Darkwa1 Background: A large percentage (16% of maternal mortality in developed countries, compared Charles Antwi-Boasiako2 to 9% in developing countries), is due to hypertensive disorders in pregnancy. The etiology of Robert Djagbletey1 preeclampsia remains unknown, with poorly understood pathophysiology. Magnesium and Christian Owoo1 calcium play an important role in vascular smooth muscle function and therefore a possible Samuel Obed3,† role in the development of preeclampsia. Daniel Sottie4 Aim: We aimed to compare serum magnesium and total calcium levels of preeclamptic and normal pregnant women at the Korle-Bu Teaching Hospital in Ghana. 1Department of Anaesthesia, Patients and methods: A comparative cross-sectional study involving 30 normal pregnant University of Ghana School of Medicine and Dentistry, 2Department and 30 preeclamptic women with >30 weeks gestation and aged 18–35 years, was conducted of Physiology, University of Ghana at the Korle-Bu Teaching Hospital. Magnesium and calcium were determined using a flame School of Biomedical and Allied Health Sciences, 3Department atomic absorption spectrometer. of Obstetrics and Gynaecology, Results: Mean serum magnesium and total calcium levels in preeclamptic women were University of Ghana School of 0.70±0.15 and 2.13±0.30 mmol/L, respectively. Mean serum magnesium and total calcium levels Medicine and Dentistry, College of Health Sciences, 4Department in normal pregnant women were 0.76±0.14 and 2.13±0.35 mmol/L, respectively. There was a of Anaesthesia, Korle-Bu Teaching statistically nonsignificant difference in serum magnesium and total calcium in preeclamptic Hospital, Accra, Ghana women compared to normal pregnant women, with p-values of 0.092 and 0.972, respectively. †Samuel Obed passed away on May Conclusion: Serum magnesium and total calcium, therefore, seem not to differ in preeclamptic 12, 2017 women compared to normal pregnant women in Ghana. Keywords: electrolytes, maternal deaths, pregnant, hypertension, Ghanaian women Introduction Preeclampsia is one of the commonest etiologies of fetal and maternal mortality and morbidity.1 The incidence of preeclampsia in developing nations is estimated to be 4–18%.2 Thus, 16% of all maternal mortality in developed countries and 9% of maternal mortalities in Asia and Africa are said to be due to hypertensive disorders in pregnancy.3 Moreover, 18% of 724 total maternal deaths at the Korle-Bu Teaching Hospital between 1984 and 1994 were due to hypertensive disorders in pregnancy, including preeclampsia.4 A worldwide perinatal and neonatal mortality rate of 10% is associated with preeclamptic disorders, with prematurity as the commonest cause of Correspondence: Ebenezer Owusu the neonatal deaths. 5 Current evidence suggests that the endothelial dysfunction seen Darkwa in preeclamptic pregnant women may persist years after the episode, and therefore Department of Anaesthesia, University of Ghana School of Medicine and Dentistry, preeclamptic women may be at high risk of cardiovascular diseases later in life. 6 College of Health Sciences, PO Box 4236, Though the etiology of preeclampsia remains unclear, many theories suggest abnor- Accra, Ghana Tel +233 24 467 0149 mal placental implantation and abnormal trophoblastic invasion as possible causes. 7 Email eoddarquah@yahoo.co.uk The molecular basis of this condition is unresolved in literature.8 It has been postulated submit your manuscript | www.dovepress.com Integrated Blood Pressure Control 2017:10 9–15 9 Dovepress © 2017 Owusu Darkwa et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. http://dx.doi.org/10.2147/IBPC.S129106 php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Powered by TCPDF (www.tcpdf.org) 1 / 1 Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 197.255.68.54 on 08-Feb-2019 For personal use only. Owusu Darkwa et al Dovepress that fluctuations in maternal serum ions may be the precipi- whom ~100 are antenatal patients. About 10,000 to 12,000 tating cause of elevated blood pressures in preeclampsia.9,10 deliveries are conducted per year at the hospital. Dietary deficiency of mineral ions has been shown to have a harmful effect on the pregnant mother and growing fetus Study population and possibly complicate preeclampsia.11 Dietary deficiency All normal pregnant and preeclamptic women with gesta- of magnesium has been established to play a role in blood tions >30 weeks and aged between 18 and 35 years inclusive, pressure regulation and hence development of preeclampsia.12 visiting the antenatal clinic at the Department of Obstetrics Evidence supporting routine magnesium supplementation for and Gynaecology, constituted the target population, except all pregnant women has not been substantiated by research, pregnant women with renal disorders, chronic hyperten- though most studies have reported reduced magnesium levels sion, gestational or preexisting diabetes mellitus, and those in pregnancy and worse levels in preeclampsia.13–18 However, on magnesium and/or calcium therapy. Preeclampsia was other studies have also reported a nonsignificant change in the diagnosed using a systolic blood pressure ≥140 mmHg and serum magnesium levels of preeclamptic women compared a diastolic blood pressure ≥90 mmHg plus a random urine to normal pregnant women.19–21 sample proteinuria ≥1+ on dipstick.31 Various studies have also reported reduced serum cal- cium levels in preeclampsia compared to normal pregnant Sample size and recruitment women.18,20–24 Calcium supplementation has been reported to The sample size was determined based on a formula by half the risk of development of preeclampsia.25 Kanagal et Charan and Biswas32 considering a mean serum magnesium al,25 in their study on calcium supplementation in pregnancy, level of 0.58 mmol/L in preeclamptic women compared to recognized that daily calcium supplementation of 1.5–2 g 0.73 mmol/L in normal pregnant women33 at a power of 80% reduced the blood pressure, prevented the development of and a 5% significance level. preeclampsia in normotensive pregnant women as well as Sixty pregnant women comprising 30 normal pregnant reduced morbidity and mortality, a finding supported by and 30 preeclamptic women with >30 weeks of gestation and Hofmeyr et al26 in their systematic review on calcium supple- between the ages of 18 and 35 years inclusive, who met the mentation in pregnant women at the community level. Other inclusion criteria were recruited consecutively and included studies, however, noted a nonsignificant difference in serum in the study after obtaining written informed consent. levels of calcium in preeclampsia compared to normotensive pregnant women.19,27–29 In a prospective study, Levine et al30 Procedures also observed that calcium supplementation during pregnancy After obtaining an informed consent, participants’ demo- does not prevent the development of preeclampsia in healthy graphic characteristics (age, weight and height) were nulliparous women. recorded on a structured data collection sheet. The blood The serum calcium and magnesium picture in preeclamp- pressure of the participants was measured using a mercury sia remains uncertain. We therefore sought to compare serum sphygmomanometer, twice in each participant 20 minutes total calcium and magnesium levels of preeclamptic and apart and averaged, noting the systolic and diastolic blood normal pregnant women at the Korle-Bu Teaching Hospital pressures, from which the mean arterial pressure was calcu- in Ghana. lated using the following formula: Patients and methods Mean arterial pressure = Diastolic blood pressure + 1/3 Study design (Pulse pressure) (1) A comparative cross-sectional study was undertaken from where Pulse pressure = systolic blood pressure – diastolic March to June 2016 at the Korle-Bu Teaching Hospital, Ghana. blood pressure Using a 5 mL syringe on a 19G hypodermic needle, 4 mL Study site of venous blood was obtained from participants’ cubital vein The Korle-Bu Teaching Hospital is the largest tertiary referral under aseptic conditions. For most serum ions, samples are to hospital in Ghana with 17 clinical and diagnostic departments be separated within 2 hours as recommended by the Clinical and a total bed capacity of 2,000, out of which 350 are in and Laboratory Standards Institute.34 Blood samples drawn the Department of Gynaecology and Obstetrics. The hospital were immediately placed in a plain test tube and sent to the has a daily outpatient attendance of ~1,500 patients, out of laboratory for analysis. At the laboratory, the blood samples 10 submit your manuscript | www.dovepress.com Integrated Blood Pressure Control 2017:10 Dovepress Powered by TCPDF (www.tcpdf.org) 1 / 1 Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 197.255.68.54 on 08-Feb-2019 For personal use only. Dovepress Serum magnesium and calcium in preeclampsia were centrifuged at 4,000 rpm for ~10 minutes to obtain the of preeclamptic women were significantly higher compared serum within 2 hours of sample collection, and subsequently to normal pregnant women. stored at –20°C prior to analysis within 24 hours of sample collection. Serum magnesium and total serum calcium were Mean serum magnesium levels of the determined using an atomic absorption spectrometer in an study participants acetylene–air flame (Variant 240FS; Varian Australia Pty Ltd, There was no signif icant difference (p=0.092) in the VIC, Australia) with reference ranges of 0.74–1.03 mmol/L mean serum magnesium levels between preeclamp- and 2.12–2.62 mmol/L, respectively. tic (0.70±0.15 mmol/L) and normal pregnant women (0.76±0.14 mmol/L), as shown in Figure 1. Statistical analysis A nonsignificant weak negative correlation was found Data obtained were stored in Microsoft® Access database between mean arterial pressure and serum magnesium lev- 2010 and analyzed with SPSS® software version 20. The els in preeclamptic women (Pearson correlation coefficient age, parity, body mass index (BMI), systolic blood pres- r=–0.089; p=0.639), as shown in Figure 2. sure, diastolic blood pressure and mean arterial pressure of the participants are presented as mean values ± SDs. The Mean total serum calcium levels of the mean serum magnesium and total calcium levels of normal study participants pregnant women and preeclamptic women were compared There was no statistically significant difference (p=0.972) using an independent t-test and are presented in a bar chart. in the mean total serum calcium levels between preeclamp- Pearson correlation coefficient was used to determine the tic (2.13±0.30 mmol/L) and normal pregnant women association between mean arterial pressure and serum cal- (2.13±0.35 mmol/L), as shown in Figure 3. cium and magnesium levels. A p-value <0.05 was considered A nonsignificant weak positive correlation was found statistically significant. between mean arterial pressure and serum total calcium lev- els in preeclamptic women (Pearson correlation coefficient Ethical issues r=0.047; p=0.806), as shown in Figure 4. The Ethical and Protocol Review Committee of the University There was a nonsignificant negative correlation between of Ghana School of Medicine and Dentistry, which is affiliated serum total calcium and serum magnesium levels in pre- to the Korle-Bu Teaching Hospital approved the study (pro- eclamptic women (Pearson correlation coefficient r=–0.328; tocol identification number: CHS-Et/M.4-P4.5/2015-2016). p=0.077), as shown in Figure 5. Results Discussion Thirty normal pregnant and 30 preeclamptic women with Similar to the findings in other studies,35,36 our study showed >30 weeks of gestation and between the ages of 18 and no statistically significant relationship between maternal age 35 years were recruited into the study. Table 1 summarizes the and preeclampsia (p=0.358). However, this contrasts with the characteristics of the pregnant women recruited. In this study, results of the study by Macdonald-Wallis et al,37 which was the mean arterial blood pressure (p<0.001), systolic blood a very large longitudinal cohort study with a sample size pressure (p<0.001) and diastolic blood pressure (p<0.001) of ~11,651 women living in a higher income region (Avon, Table 1 Summary of participants’ characteristics Parameter Preeclamptic women Normal pregnant women p-value Mean±SD Mean±SD n=30 n=30 Age, years 30.97±5.51 29.93±2.60 0.358 Parity 1.70±1.42 1.13±1.41 0.567 BMI, kg/m2 32.03±7.52 30.50±5.50 0.374 SBP, mmHg 170.13±23.69 116.47±13.38 0.000* DBP, mmHg 106.30±18.79 67.57±8.54 0.000* MAP, mmHg 126.20±20.86 83.87±8.85 0.000* Note: *Significant at p<0.05. Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure. Integrated Blood Pressure Control 2017:10 submit your manuscript | www.dovepress.com 11 Dovepress Powered by TCPDF (www.tcpdf.org) 1 / 1 Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 197.255.68.54 on 08-Feb-2019 For personal use only. Owusu Darkwa et al Dovepress 0.9 as inclusion of women with known diabetes, known chronic 0.8 p=0.092 hypertension and gestational diabetes. The BMI calculation in 0.7 their study was also based on self-reported recall information of prepregnancy weight and therefore there is a possibility of 0.6 information bias. There also could be differences in the diet 0.5 of the studied population. These factors may account for the 0.4 differences in their findings compared to ours. 0.3 The blood pressures (mean systolic, mean diastolic and 0.2 mean arterial pressures) of the preeclamptic women were sig- nificantly elevated compared to the normal pregnant women 0.1 (p<0.001), as expected per the case definition. Mean arterial 0 pressure has been observed to be predictive of preeclampsia, Preeclamptic Normal pregnant women women even though other studies have reported otherwise.42 Magnesium and calcium are important cofactors for vari- Category ous enzymatic processes and water balance in cells.43 These Figure 1 Mean serum magnesium levels of preeclamptic and normal pregnant women. trace elements play an essential role in vascular smooth England), as compared to our sample population. Addition- muscle tone and contraction, and hence they are vital in blood ally, they considered the number of fetuses and the sex of pressure regulation.44 the fetuses being carried by the women, as well as the edu- Various studies have reported a decrease in serum mag- cational status of the women, factors we did not consider in nesium levels as a possible etiology of preeclampsia.13,14,16–18 our study. Therefore, differences in the study design and the This evidence is supported by the usefulness of magnesium characteristics of the patient population studied may possibly sulfate therapy for prophylaxis and treatment of seizures account for the differences in the results. associated with preeclampsia/eclampsia.45 However, this view We also noted a nonsignificant relation between pre- is not universally accepted, as a Cochrane review involving eclampsia and BMI (p=0.374), as noted by Onyegbule et al,38 2,689 women from seven selected randomized and quasi- even though other studies have shown a strong association randomized trials found no high-quality evidence to support between BMI and preeclampsia.39–41 The findings of Pooro- the beneficial effect of dietary magnesium supplementation lajal and Jenabi39 were derived from a meta-analysis, while in preventing the development of preeclampsia in pregnant ours is a case–control cross-sectional study, and this may women.46 therefore account for the differences in results. In contrast Dietary deficiency of calcium, with consequent reduced to our study, Hauger et al41 conducted a large-sample-size serum calcium levels, has been implicated as a cause of pre- multicenter study with possible confounding factors such eclampsia in some studies.18,25,26,47,48 This has been explained 2 200.00 R linear =0.008 p=0.639 180.00 160.00 140.00 120.00 100.00 80.00 0.20 0.40 0.60 0.80 1.00 Serum magnesium level (mmol/L) Figure 2 Correlation between serum magnesium levels and mean arterial pressure in preeclamptic women. 12 submit your manuscript | www.dovepress.com Integrated Blood Pressure Control 2017:10 Dovepress Powered by TCPDF (www.tcpdf.org) 1 / 1 Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 197.255.68.54 on 08-Feb-2019 For personal use only. Serum magnesium levels (mmol/L) Mean arterial pressure (mmHg) Dovepress Serum magnesium and calcium in preeclampsia 2.5 a universal finding in literature.1,20,21,55 Various studies from p=0.972 different regions worldwide have reported varying results 2 concerning the role of these trace elements in the etiology of preeclampsia.17,18,56,57 In this study, we observed no sta- tistically significant difference in mean total serum calcium 1.5 and magnesium levels of preeclamptic women compared to normal pregnant women (p=0.092), as found in a study by 1 Magri et al.57 Similar studies conducted, including those done in sub-Saharan Africa using the same method of assay (atomic 0.5 absorption spectrophotometry), in determining serum cal- cium and magnesium levels also show varying results.38,58,59 Ugwuja et al,58 in a study conducted among Nigerian women 0 Preeclamptic Normal pregnant using atomic absorption spectrophotometry for assaying women women serum calcium and magnesium, found no significant dif- Category ference in serum calcium but significantly reduced serum Figure 3 Mean total serum calcium levels of preeclamptic and normal pregnant women. magnesium in preeclamptic women as compared to normal Note: Error bars indicate the confidence interval of the mean of serum calcium levels. pregnant women. Another study conducted among Sudanese women using atomic absorption spectrophotometry for assay- R2 linear =0.002 ing serum calcium and magnesium found a decreased serum 200.00 p=0.806 calcium level and an increased serum magnesium level59 180.00 in preeclamptic women as compared to normal pregnant women. These studies, including ours, were conducted in 160.00 sub-Saharan Africa using the same method of assay for both 140.00 ions, but the findings were different. It is therefore possible that the differences in the findings 120.00 may be attributed to not only differences in the method of 100.00 assay of serum ions but also differences in dietary habits, genetic pools, as well as the social and economic lifestyle 80.00 factors of the populations studied. The dietary history 1.00 1.50 2.00 2.50 3.00 and socioeconomic status of the participants in this study Serum calcium level (mmol/L) were, however, not elucidated. Additionally, differences in Figure 4 Correlation between total serum calcium levels and mean arterial sample size may also account for the observed differences pressure in preeclamptic women. in findings. by the vasoconstrictive effect caused by reduced serum cal- A nonsignificant negative correlation was observed cium levels.1,20–24 Stimulation of 1,25-dihydroxycholecalcif- between serum total calcium and serum magnesium levels erol has been implicated in this vasoconstrictive mechanism.18 in preeclamptic women (Pearson correlation coefficient This concept of a reduced serum calcium level in preeclampsia r=–0.328; p=0.077) in contrast to the findings of Ephraim is not accepted universally.19,27,29,30,49 This is because other et al,60 who noted a nonsignificant positive correlation studies in preeclamptic women have noted relatively reduced between serum calcium and serum magnesium levels. A non- 1,25-dihydroxycholecalciferol levels compared to normal significant weak negative correlation was observed between pregnant women,50 with consequent increase in parathyroid mean arterial pressure and serum magnesium levels in pre- hormone levels,1,20 causing reabsorption of calcium from the eclamptic women (Pearson correlation coefficient r=–0.089; distal renal tubules and the intestines51–53 and therefore causing p=0.639). A nonsignificant weak positive correlation was no significant change in the serum calcium levels. Parathyroid observed between mean arterial pressure and serum total hormone also causes renin release with subsequent vasocon- calcium levels in preeclamptic women (Pearson correlation striction and sodium retention in preeclamptic women.54 coefficient r=0.047; p=0.806). Therefore, total serum calcium Therefore, hypomagnesemia and hypocalcemia as etio- and serum magnesium may be weak predictors of mean arte- pathologic factors in the development of preeclampsia are not rial pressure in preeclamptic women. Integrated Blood Pressure Control 2017:10 submit your manuscript | www.dovepress.com 13 Dovepress Powered by TCPDF (www.tcpdf.org) 1 / 1 Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 197.255.68.54 on 08-Feb-2019 For personal use only. Mean arterial pressure (mmHg) Total serum calcium (mmol/L) Owusu Darkwa et al Dovepress 3.00 R 2 linear =0.108 p=0.077 2.50 2.00 1.50 1.00 0.20 0.40 0.60 0.80 1.00 Serum magnesium level (mmol/L) Figure 5 Correlation between serum magnesium levels and total serum calcium levels in preeclamptic women. Conclusion 8. Roberts J, Cooper D. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001;357(9249):53–56. There was no significant difference in the mean serum levels 9. Hanisch CG, Pfeiffer KA, Schlebusch H, Schmolling J. Adhesion of magnesium and total calcium between preeclamptic and molecules, activin and inhibin – candidates for the biochemical pre- normal pregnant women. diction of hypertensive diseases in pregnancy? Arch Gynecol Obstet. 2004;270(2):110–115. Total serum magnesium and calcium therefore seem not 10. Bussen S, Sütterlin M, Steck T. Plasma endothelin and big endothelin to differ in preeclamptic women in comparison with normal levels in women with severe preeclampsia or HELLP-syndrome. Arch Gynecol Obstet. 1999;262(3–4):113–119. pregnant Ghanaian women. 11. Raman L, Shatrugna V. Nutrition during pregnancy and lactation. In: Mahtab SB, Prahlad RN, Vinodini R, editors. Textbook of Human Nutri- Acknowledgments tion. New Delhi: IBH; 2002:509. 12. Sarma P, Gambhir S. Therapeutic uses of magnesium. Indian J Phar- The authors express their sincere gratitude to all the patients macol. 2005;27:7–13. who participated in this study. The authors also convey special 13. Roberts JM, Myatt L, Spong CY, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Mater- thanks to Raymond Essuman and George Aryee for their nal-Fetal Medicine Units Network. Vitamins C and E to prevent immense support. complications of pregnancy-associated hypertension. N Engl J Med. 2010;362(14):1282–1291. Disclosure 14. Catov JM, Nohr EA, Bodnar LM, Knudson VK, Olsen SF, Olsen J. Association of periconceptional multivitamin use with reduced risk The authors report no conflicts of interest in this work. of preeclampsia among normal-weight women in the Danish national birth cohort. Am J Epidemiol. 2009;169(11):1304–1311. 15. Harrison V, Fawcus S, Jordaan E. Magnesium supplementation and References perinatal hypoxia: outcome of a parallel group randomised trial in 1. Sukonpan K, Phupong V. Serum calcium and serum magnesium in pregnancy. BJOG. 2007;114(8):994–1002. normal and preeclamptic pregnancy. 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