Comparative Evaluation of Serum Calcium and Magnesium Level in Preeclamptic and NonPreeclamptic Women in a Tertiary Hospital in Southern Nigeria
European Scientific Journal April 2018 edition Vol.14
Comparative Evaluation of Serum Calcium and Magnesium Level in Preeclamptic and Non- Preeclamptic Women in a Tertiary Hospital in Southern Nigeria
Allagoa DO. BMedsc (Pharm) MBBS 0
CERT ART 0
Dip HMS 0
Consultant Obstetrician/Gynaecologist 0
Federal Medical Centre Yenagoa 0
Bayelsa State 0
Nigeria Agbo OJ. MBBS 0
Consultant Obstetrician 0
Federal Medical Centre Yenagoa 0
Bayelsa State 0
Nigeria Orluwene CG. 0
0 MBBS,FWACS, Consultant Chemical Pathologist, University of Port Harcourt Teaching Hospital , Port Harcourt, Rivers State , Nigeria
Background: Calcium and magnesium are two micronutrients whose role in the development of preeclampsia has been investigated over the years. There is paucity of studies on the role of serum levels of calcium and magnesium in the development of preeclampsia in south-south Nigeria. Objective: Our study evaluated the serum level of calcium and magnesium in preeclamptic and non preeclamptic women in a Tertiary Hospital in southsouth Nigeria. Methodology: We carried out a comparative study in which 52 preeclamptic and 52 non preeclamptic women, who satisfied the eligibility criteria, were enrolled for the study. Data entry and statistical analysis was done using statistical software (IBM SPSS® for windows version 21.0). Data were analyzed for mean and standard deviation. Comparison of serum levels of elements between the two groups was performed by student t-test, and P value < 0.05 was considered as statistically significant. Results: The serum calcium level was statistically lower in the women who developed preeclampsia compared to those who did not (8.37±0.91 mg/dl vs 9.33±1.15mg/dl, p<0.001). The serum magnesium level was not statistically different between women who had preeclampsia and those who did not (1.79±0.24mg/dl vs 1.88±0.37mg/dl, p = 0.102). The systolic and diastolic blood pressure showed a significant negative correlation with serum calcium
level, unlike serum magnesiun level in those that had preeclampsia.
Conclusion: This study showed that women who developed preeclampsia
demonstrated reduced serum calcium level and no reduction in serum
magnesium level. This study support the hypothesis that hypocalcaemia,
unlike hypomagnecaemia, is a possible aetiology of preeclampsia.
Preeclampsia remains a major obstetrics problem all over the world
accounting for a large percentage of maternal and perinatal morbidity and
(World Health Organization, 2005)
. The World Health Organization
estimates that its incidence is 7 times higher in developing countries than in
developed countries and a woman in developing country is 300 times more
likely to die from preeclampsia and eclampsia
(Engender Health, 2007; Gaym
et al., 2011)
Preeclampsia is a common and life threatening complications of
pregnancy. The aetiology is not fully understood, but yet treatment modalities
are offered. Many theories have been put forward in an attempt to explain the
aetiology of preeclampsia; however, the acceptable theories include abnormal
trophoblastic tissue invasion of uterine arteries, immunological theory,
endothelia cell activation, dietary deficiency, and genetic factors
2007; Kenny, 2011; Miller, 2007)
The relationship between preeclampsia and nutritional deficiencies has
been well established; studies have persistently and consistently shown that a
relationship exist between the two
(Belinzn et al., 1988; Hofmer et al., 1994;
Onyegbule et al., 2014; Carroli et al., 1994)
. An inverse relationship between
calcium intake and hypertensive disorders of pregnancy was first reported in
(Hofmer et al., 2010)
. This was based on the observation that Mayan
Indians in Guatemala who traditionally soak their corn in Lime before eating
had a high calcium intake and low incidence of preeclampsia
(Hofmer et al.,
. The results of clinical trials showed the aggravation of hypertensive
complication and the change in concentration of various trace elements
(Belinzn et al., 1988; Hofmer et al., 1994; Onyegbule et al., 2014; Carroli et
al., 1994; Hofmer et al., 2010)
. Calcium and magnesium have a relaxant
effects on blood vessels of pregnant women and changes in the
concentration of these elements can lead to alteration of blood pressure
(Carroli et al.,1994; Hofmer et al., 2010)
. The depletion
of tissue stores of magnesium might explain why eclamptic patients tolerate
large doses of magnesium as used in contemporary treatment
(Sibai; Duley et
. A very low prevalence of preeclampsia has been reported in
Ethiopian though a developing country these may be due to the high calcium
level in their diets
(Hofmer et al., 2010)
Deficiencies of trace elements like calcium and magnesium have been
implicated in the aetiology of preeclampsia. There are few studies done to
determine the role of serum calcium and magnesium in South-south Nigeria.
This study therefore proposes to determine the mean serum levels of calcium
and magnesium levels in preeclamptic and healthy women in a tertiary
Hospital in South-south, Nigeria. This study also aimed at determining if the
difference in serum levels of the trace elements were statistically significant
and contributes to the understanding of the role of serum calcium and
magnesium in the development of preeclampsia.
This study was carried out in the University of Port Harcourt Teaching
Hospital. It is a 650-bed hospital located at Alakhahia in Obio -Akpor local
government area of Rivers State, South-South Nigeria, about 15 kilometers
from Port Harcourt city along the East-West road. It is a tertiary health center
that provides all levels of health care services for Rivers, Bayelsa, Delta, Imo,
Abia, and Akwa-ibon States. The obstetrics and gynaecology department is a
key department in the hospital with 18 Consultants staff. On the average,
between 400 and 450 pregnant women are booked for antenatal care services
in the hospital every week, and primidravidae constitute about 41% of total
attendance. Follow up attendance rate is between 250 and 300 patients per
week. The delivery rate in the hospital is about 3500 which gives an average
monthly of 290 deliveries. The hospital has a chemical pathology department
staffed by consultants, resident doctors, Laboratory scientists, and interns.
Over 40 different tests are conducted in the chemistry laboratory including
serum calcium and magnesium.
This was a comparative case study designed to evaluate the levels of
serum calcium and magnesium in pregnant women with preeclampsia and
those non preeclamptic in the University of Port Harcourt Teaching Hospital.
This study was performed from 1st of July 2015 to 22nd of February 2016. The
control and study group was chosen from women attending ante natal care in
the University of Port Harcourt Teaching Hospital. The control group was
chosen from women who fulfilled the inclusion criteria and were followed up
from booking till delivery, but did not develop preeclampsia in the third
trimester. On the other hand, the study group was those that were followed up
from booking and on development of preeclampsia in the third trimester and
that fulfilled other selection criteria which were enrolled in the study.
A proforma developed for the study was used to record the
sociodemographic characteristics, clinical and laboratory data of the patients. The
content of the questionnaire include age, marital status, occupation,
educational status, religion, parity, booking status, last menstrual period,
gestational age, past history of diabetes or hypertension, family history of
diabetes or hypertension, presence or absence of pedal oedema, serum calcium
level, serum magnesium level, onset of delivery, mode of delivery, birth
weight, Apgar score, and admission into special care baby units.
1 All those who developed preeclampsia based on: Blood pressure equal to
or greater than 140/90 mm Hg on two occasions: 6 hours apart and proteinuria
greater than 300mg in 24 hours urine sample or one plus of protein in 2
midstream urine sample collected 6 hours apart in the 3rd trimester.
2 Singleton fetus
3 Gestational age: third trimester
5 No history or evidence of urinary tract infection
6 Age range 18 to 35 years
7 Non diabetics
1 Multiple pregnancies
3 Pregnancy with renal disease
4 Gestational trophoblastic diseases
5 Chronic hypertension
6 Pregnancy with heart disease
7 Patients already on magnesium sulphate
8 Maternal age greater than 35 years
Sample Size Determination
Consequently, the sample size was calculated using the formula for
comparison of two means:
n= minimum sample size required
U=one sided percentage point of the normal distribution corresponding to
100% minus the power. Thus, the power is 90%, and then U=1.28, V=
percentage point of the normal distribution corresponding to the two sided
significance level. Thus at 5% significance level, V=1.96
SD1= standard deviation in study group= 0.37
SD2= standard deviation in control group= 0.69
U1= mean of observation in study group= 1.92
U2= mean of observation in control group=2.29
Therefore, a minimum sample size of 47 patients is required in each group.
Adjusting for a drop out of 10%, this study will require a total of 104 patients
(52patients in each group).
Data Collection And Processing
The participants in this study were followed up from booking in the
second trimester (the minimum gestational age at booking was 16 weeks).
Also, informed consent was obtained from each participant before recruitment
into the study. A detailed history was taken to ensure each patient fulfilled the
selection criteria. Data regarding socio-demographic characteristics, clinical,
family history, and laboratory results were recorded in the Proforma. A
through clinical examination was done for each patient. The Height and weight
of each participant was measured (using a weighing scale ZT-120, METLAR)
and the body mass index was calculated by dividing the weight in
kilogrammes by the square of the height in meters.
Those in the control group were all normotensive from booking and
did not develop preeclampsia. For those in the study group which were
followed up from booking and the development of preeclampsia in the third
trimester for the first time, the fulfillment of the selection criteria were
recruited for the study. Patients in both groups were followed up till delivery.
Blood pressure was measured with the use of manual
sphygmomanometer while the patient was in supine position on a couch with
a left sided tilt. An appropriate size cuff that covers at least 2/3rd of the upper
arm was used. The systolic blood pressure was taken at the first point the sound
was heardwhile, the diastolic blood pressure was taken as Korotkoff V. (the
absence of sound). A patient was said to be hypertensive when her blood
pressure was equal to or greater than 140/90 mmHg measured at least 6 hours
apart. Urine collection was done in the ante natal clinic between 8 to 9 am.
Urine samples were collected under the supervision of trained Nurses. Patients
were given clean, dry, wide-mouthed, leak-proof containers with their names
and number on it. Patients were instructed to clean their vulva with copious
clean water, and then part their labia and the first part of the urine voided and
to collect the next stream of urine into the urine containers provided. Samples
were analyzed for protein estimation using dip stick. Protein estimation was
made based on the colour change of the dip stick compared to the
corresponding colour chart on the reagent container. The diagnosis of
proteinuria was made when two samples of mid-stream urine collected, at least
four hours apart, showed one or more plus of albumin. Urine microscopy
culture and sensitivity test was routinely done in suspicious cases to exclude
infection. Therefore, a patient was said to be preeclamptic when her blood
pressure was equal to or greater than 140/90mmHg measured at least six hours
apart accompanied by proteinuria of at least one plus.
Blood samples (5mls) was taken from the ante cubital vein and sent to
the laboratory for calcium and magnesium estimation. Blood samples were
taken for women in the control group at the time of presentation in the labour
ward after an informed consent have been obtained. For patients with
preeclampsia, blood samples were collected at the time the diagnosis was first
made and before the administration of magnesium sulphate. Then they were
followed up till delivery.
At the laboratory, the samples were centrifuged to get the serum which
was stored in the refrigerator until the time of analysis. Serum calcium
measurement was done using quantitative spectrophotometric analysis. Serum
albumin binds to calcium was used to calculate the correct serum calcium level
as shown in this formula below.
Corrected total calcium (mg/dl) = Total calcium measured (mmol/L) +
Serum magnesium level Analysis was done by the direct calmagite method.
Serum calcium was analyzed using an automated electrolytes analyzer
(FT1000 Automatic chemical analyzer, fortune limited, Chengdu, China).
Magnesium was analyzed using the kit manufactured by Teco Diagnostics,
At birth, data were collected regarding onset of labour, mode of
delivery, birth weights, Apgar score, information on whether the baby was
admitted into the special care baby unit or were not entered into the Proforma,
and the development of any complication.
Statistical analysis was done using statistical software (IBM SPSS® for
window version 21.0). Data were analysed for mean and standard deviation.
Comparison of serum levels of calcium and magnesium between the two
groups was performed by student t-test, and P value <0.05 at 95% confidence
interval was considered as statistically significant.
A total of one hundred and four women were enrolled in the study. The
socio- demographic characteristics of the patients were shown in tables 1, 2, 3
and 4. In the cases group, the age range of women was 18 to 35 years and the
mean age was 27.58 ± 7.34 years. While in the control group, the age range of
women used in this study was 18 to 35 years and the mean age was 26.71±4.21
years. The difference was not statistically significant, and the P value was
0.45. In the cases group, 11% were singles while 87% and 2% were married
and divorced respectively. In the control group, 8% were singles while 88%
and 4% were married and divorced respectively. In the cases group, 27% had
primary education, while 44% and 29% were educated up to secondary and
tertiary level respectively. In the control group, 11.5% were educated up to
primary level, while 46.2% and 42.3% had secondary and tertiary education
respectively. In the cases group, 94.2 % of them were Christians and 5.8%
Muslems. In the control group, 90.4% were Christians and 9.6% Muslems.
The mean gestational age was 36.54±2.69 weeks for preeclamptic
patients. In the non preeclamptic group, the mean gestational age was
38.67±1.10 weeks. There was a significant difference between the two groups.
The p value was 0.01. The mean body mass index range of the cases group
was 28.09±3.50 Kg/m2. The mean body mass index of the control group was
26.42±2.42Kg/m2. There was a statistical difference in body mass index
between the two groups. The p value was < 0.01. The mean systolic blood
pressure of the cases group was 158.88±11.80 mmHg. The mean systolic
pressure of the control group was 113.65±7.15 mmHg. There was a statistical
difference in systolic blood pressure between the two groups. The p value was
0.01. The mean diastolic blood pressure for the cases group was
101±8.20mmHg. The mean diastolic blood pressure of the control group was
71.35±6.57mmHg. There was a statistical difference in diastolic blood
pressure between the two groups. The p value was 0.01.
The mean serum calcium level in preeclamptic women was 8.37±0.91
mg/dl. The mean serum calcium level in non preeclamptic women was
9.33±1.15mg/dl. The p value was 0.01. There was a statistical difference in
the mean serum calcium level between the two groups. The mean serum
magnesium level in preeclamptic women was 1.79±0.24mg/dl. The mean
serum magnesium level in non preeclamptic women was 1.88±0.37mg/dl. The
p value was 0.10. There was no significant difference in mean serum
magnesium level between the two groups.
There was a negative correlation between systolic blood pressure and
serum calcium level. Pearson correlation = - 0.335, p< 0.01. There was also a
negative correlation between diastolic blood pressure and serum calcium level.
Pearson correlation = - 0.256, p< 0.01. There was no correlation between the
systolic blood pressure and serum magnesium level. Pearson correlation =
0.105, p value was 0.300. There was no correlation between diastolic blood
pressure and serum magnesium level. Pearson correlation = - 0.170, p value
The onset of labour was spontaneous in 32.7% of patients with
preeclampsia, while it was 73.1% in the non preeclamptic group. Labour was
induced in 28.8% of the study group, while in the control group, 15.4% of
women had their labour induced. In the control group, 38.5% had no labour
while in the control group 11.5% had no labour. In the study group, 44.2% had
vaginal delivery as against 88.5% in the control group. Caesarean section was
performed for 55.8% of women in the cases group, while 11.5% of women in
the control group had caesarean section as their mode of delivery. The mean
birth weight in the preeclamptic women was 2.71±0.70Kg. The mean birth
weight in non preeclamptic women was 3.10±0.43Kg. The p value was 0.01.
There was significance in birth weight between the two groups. In the cases
group, 30.8% of babies were admitted in the special care baby unit, while in
the control group, 7.7% were admitted.
Calcium and magnesium are elements which are deficient in pregnant
women in developing countries. This usually occurs due to reduced dietary
intake which is common in developing countries. Our study showed a
statistical significant lower calcium level with no significant changes in
This study did not show any statistical significance in age between the
two groups, which was also noted by another study in pregnant women in
Abakaliki, South-East Nigeria. However, the study reported no significant
difference in age between preeclamptic and healthy women
(Ugwuja et al.,
. Earlier studies of Onyegbule et al. (2014) and Akinloye et al. (2010)
were keeping with the findings of our study. However, in another work by
Kanagal et al. (2014) in India, there was a significant difference in age between
preeclamptic patients and non preeclamptic patients. This may be due to
difference in age, diet, and study population. Increase in maternal age is a
wellestablished risk factor for the development of preeclampsia
(Jido & Yakasai,
2014; Anorlu et al., 2005)
. As parity increases, age also increases.
Obesity predisposes a woman to the development of preeclampsia and
a relationship between increasing body mass index and the risk of
preeclampsia is well established
(Jido & Yakasai, 2014; Kaklina et al., 2009)
The study revealed a very strong association between the development of
preeclampsia and body mass index. Akinloye et al also found a significant
higher body mass index in the preeclamptic. The finding of this work was
consistent with previous study (Jido & Yakasai, 2014). However, the result of
this study was not keeping with the findings of Ugwujaet al. (2016) which
showed a significantly higher body mass index among non preeclamptic
women. The study concluded that the reason for the higher body mass index
in normotensive patients is obscure. However, genetic factors may be
This study showed that the patients who had preeclampsia have their
babies delivered at a lower gestational age. The reason being that the ultimate
cure for preeclampsia is delivery to prevent the development of maternal or
fetal complications. The decision to deliver depends on the severity of the
disease, gestational age, maternal and fetal complications. Thus, delivery is
not always in the interest of the baby
(Miller, 2007; Repke & Sibai, 2009)
The result of this study is consistent with an earlier report (Kanagal et al.,
2014). The report of this study is not in agreement with a similar study
(Ugwuja et al., 2016)
that reported no significant difference between pregnant
women with preeclampsia and non preeclamptic in terms of gestational age at
delivery. Similar reports in the past had same findings
(Gol Mohammed et al.,
2008; Naser & Ziad, 2000)
The results from this study showed a mean systolic blood pressure of
158.88±11.80 mmHg and a mean diastolic blood pressure of 101±8.20 mmHg
in preeclamptic patients in contrast to a mean systolic blood pressure of
113.65±7.15 mmHg and a mean diastolic blood pressure of 71.35±6.57mmHg
in control group. This was consistent with an earlier investigation by
Sukonpan et al. (2005) who reported a mean systolic blood pressure of
155.50± 12.18 mmHg and a mean diastolic blood pressure of 108.18±10.89
mmHg in preeclamptic patients, and also a mean systolic and diastolic blood
pressure of 108±6.50mmHg and 68.60±8.19 mmHg in the control group
respectively. The slight differences may be due to ethnic differences. The
implication of this is that the pathogenesis and severity of complications
following preeclampsia varies from one region to the other
(Akinloye et al.,
The birth weight of babies was significantly lower in preeclamptic
patients. The reason is that hypertensive disorders during pregnancy are
associated with vasculopathy, which also affects the placenta and the relative
placenta insufficiency wound. However, this is also expected to affect the fetal
birth weight to some degree. There were similar findings in earlier studies
(Jido & Yakasai, 2014; Naser & Ziad, 2000; Sukonpan & Phupong, 2005)
In this study, the mean serum level of calcium in the control group was
9.33±1.15 mg/dl, while the mean serum calcium level in the cases group was
8.37±0.91 mg/dl. Calcium is an important element as it is necessary for muscle
contraction and neuronal activity. The blood pressure changes evident in
preeclampsia can be attributed to the change in serum calcium level. Decrease
in serum calcium levels led to an increase in intracellular calcium. This led to
constriction of blood vessels and an increase in vascular resistance and also a
resultant increase in blood pressure
(Sukonpan & Phupong, 2005)
The major finding in this study was the significant lower level of mean
serum calcium level in preeclamptic women 8.37±0.91 mg/dl compared to non
preeclamptic women 9.33±1.15 mg/dl. Akinloye et al. (2010) had a similar
finding which was supported by other previous reports
(Kanagal et al., 2014;
Kumru et al., 2003; Abdallah & Abdiabo, 2014)
. However, this was in
disagreement with the study by Gol Mohammed et al. (2008) who reported
that there was no difference in the level of serum calcium level between
preeclamptic and non preeclamptic women. The difference in serum calcium
levels obtained in different studies may be due to the difference in the study
design, analytical technique, difference in population characteristics such as
age, race, ethnicity, socio-economic status as well as country and region of
residency (Essom et al., 2012). This study supported the hypothesis that
hypocalcaemia might be a factor in the development of preeclampsia.
The serum magnesium level in this study was 1.79±0.24mg/dl for the
preeclamptic women. The mean serum magnesium level was 1.88±0.37mg/dl
for non preeclamptic women. Decreased in serum magnesium level has been
considered as the cause of preeclampsia. The success of magnesium therapy
as a treatment for eclamptic seizure and the known effect of magnesium on
vascular smooth response in-vitro suggested that magnesium might be
deficient in women with preeclampsia
(Jido & Yakasai, 2014)
An important finding in this study shows that there was no difference
in the mean serum magnesium level (1.79±0.24mg/dl) in the preeclamptic and
non preeclamptic (1.88±0.37mg/dl). The findings of this study are in
accordance with previous studies
(Gol Mohammed et al., 2008; Kumru et al.,
. This was supported by an earlier work by Kanagal et al in Indian where
most of the patients used for the study were from the lower class strata with
poor dietary consumption of calcium and magnesium rich food. Thus, the
findings in this study were not in agreement with previous studies
et al., 2014; Akinloye et al., 2010)
. The difference in value of magnesium
obtained in various studies may be due to variation in the study population and
This study has potential limitations and issues attracting criticism.
First, the dietary intake of preeclamptic women was not taken prior to the
commencement of the study to ascertain their calcium and magnesium level.
Another limitation of this study is the non-use of quantitative method in
detecting proteinuria. The direct (Calmagite) method which is easier and
cheaper was used in this study instead of the ion-selective electrode which is
better, but expensive in the analysis of serum calcium and magnesium levels.
However, findings from this study remain relevant and add to evidence on the
1. This study showed that in preeclamptic women, serum calcium is
2. This study support the hypothesis that hypocalcaemia is a possible
aetiology of preeclampsia.
3. The study revealed that in preeclamptic women, serum magnesium
level is not significantly reduced.
4. This study did not support the hypothesis that hypomagnesaemia is a
possible cause of preeclampsia.
5. There was a negative correlation between serum calcium level and
systolic or diastolic blood pressure.
6. There was no negative correlation between serum magnesium level
and systolic or diastolic blood pressure.
Based on the results obtained from this study, the following recommendations
1. Educating women of reproductive age on the importance of micronutrients
in the prevention of preeclampsia.
2. Routine screening and close surveillance of micronutrients, especially
calcium during antenatal period.
3. Dietary supplementation with calcium should be done at least in susceptible
women, especially in developing countries.
4. More studies should be carried out in this field.
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