Clinical Status of Pregnancy-Induced Hypertension and Pre-Eclampsia among Sudanese Women

Objective: The present study has been conducted with the aim of determining the clinical status of gestational hypertensive disorders in Sudan. Methods: An analytical case-control, comparative and descriptive cross-sectional, hospital-based study was conducted at Omdurman Maternity Hospital (OMH). It included 228 cases of gestational hypertensive disorders. Data were collected through interviews, questionnaire, and admission records and analyzed statistically. Results: The clinical status of pregnancy-induced hypertension and pre-eclampsia among Sudanese women has been estimated. Spontaneous pregnancies were 94.6% of the cases. Multigravida were 50.4% of pregnant Sudanese women presenting at OMH, 20.7% of them had a history of gestational hypertensive disorders and 18.1% had a history of miscarriage. Among the patients admitted with gestational hypertensive disorders 75% developed preeclampsia, 91% has shown non-syndromic complications and 52.2% were asymptomatic. Conclusion: Maternal age between 18-40 years, nulliparous primigravida or multigravida with long Original Research Article Osman et al.; JPRI, 33(62A): 167-176, 2021; Article no.JPRI.80390 168 latency period and history of miscarriage are the commonest risk factors of hypertension complication during pregnancy, including preeclampsia, in Sudan. Significantly lower serum calcium and/or higher serum magnesium are associated with preeclampsia, syndromic HELLP is a rare association. Patient awareness is critical for early detection and prevention of disease progression.


INTRODUCTION
Pregnancy is a reproductive process in which one growing fetus, or more, develops inside the maternal uterus [1]. Normal uneventful pregnancy describes the normal physiological pattern of events in which the mother remains fit and well throughout the gestation period [2].
Physiological changes occur in a woman's body systems to varying degrees, and intensities. These include the cardiovascular, respiratory, genitourinary, and musculoskeletal systems [3].
Hypertensive disorders remain a major global health issue for women and their feti [4]. The classification of hypertensive disorders mainly depends on the time of the onset of the disorder, whether it occurs before or after 20 weeks of gestation [5]. The presence of proteinuria is the determining factor of preeclampsia [6]. Hypertensive disorders in pregnancy is directly related to maternal and fetal mortality and morbidity [7]. They are clinically defined as a change in blood pressure recorded at two different occasions; systolic blood pressure at 140 mmHg or more [8]; diastolic blood pressure at 90 mmHg or more [9]. This elevation in blood pressure is mainly responsible for the adverse maternal and fetal outcomes [7]. However, with the appropriate prenatal care and observation of women for signs of preeclampsia, instant delivery can resolve this disorder and reduce the number and the extent of poor outcomes [10]. Therefore, these adverse outcomes of serious materno-fetal morbidity and mortality are avoidable [11].
The pregnancy-induced hypertension (PIH) and preeclampsia both cause an increase in the blood pressure which occurs after 20 weeks of gestation. In preeclampsia there is a systemic involvement and proteinuria which can result in visual, renal, and even liver problems [12]. Preeclampsia is more serious than gestational hypertension or pregnancy induced hypertension and is responsible for maternal and prenatal mortality [13]. Gestational hypertension has no systemic features as seen in preeclampsia [14], however, it also needs appropriate management during pregnancy and labor [15].
Chronic hypertension is hypertension diagnosed before 20 weeks of gestation or before pregnancy [16]. Chronic hypertensive subjects have a higher risk of developing superimposed preeclampsia during pregnancy [17]. Women with superimposed preeclampsia have similar neonatal outcomes but more maternal complications than women with preeclampsia [18].
The clinical manifestations of preeclampsia vary from patient to patient and may be symptomatic or asymptomatic [19]. The most characteristic symptoms are headache [20], and fever with or without visual disturbance [21]. Additional symptoms can be right upper quadrant pain, due to liver ischemia, and lower abdominal pain if placental abruption, occurs [22]. Convulsion can occur when preeclampsia is complicated and develops to eclampsia when vascular dysfunction affects vasculature of the brain [23]. Another complication of preeclampsia is syndromic HELLP which stands for hemolysis, elevated liver enzymes, and low platelet count [23].
Maternal urine examination for the protein spots (using urinary dip stick for protein) confirms the diagnosis with the elevation in measurement of both systolic and diastolic blood pressure [24,25]. Monitoring of women with pre-eclampsia includes the assessment of hematological parameters, hemoglobin and platelets, to detect exacerbation of the disease into the more serious eclampsia or HELLP syndrome [26]. Biochemical tests of hepatic and renal function assess the complexity of the case [27], disease progressions and early diagnosis of deterioration in the maternal clinical situation [28].
The status of gestational hypertensive disorders in Sudan is not reported. The present study has been conducted with the aim of determining the clinical status of gestational hypertensive disorders in Sudan.

Study Design and Study Area
Analytical, case-control, comparative study and descriptive, cross-sectional, hospital-based study were conducted at Omdurman Maternity Hospital.

Sample Size Estimation
The sample size was calculated using (Raosoft Software) computer program at confident level (95%) for cross sectional study. Unmatched case control sample size calculator, for case control study, were used and the number of patients with preeclampsia in OMH during 2015 was obtained from the hospital Statistics Record.

Inclusion Criteria
All clinically diagnosed cases of eclampsia, preeclampsia, HELLP, and post-partum condition of eclampsia, preeclampsia and HELLP.

Exclusion criteria
All pregnant women clinically diagnosed with nephritic syndrome or any deterioration in renal function, pregnant women with chronic hypertension and on antihypertensive therapy before gestation and all pregnant women with diabetes mellitus or autoimmune diseases.

Study Duration
The study was conducted during the period from June 2016 to October 2017.

Data Collection Techniques and Design
Data were collected by approaching patients with personal interviews, telephone interviews, and face to face self-administrated questionnaires. Clinical records of the direct observation of the Senior Attendant Registrar at the time of admission were also collected. Data Collection Forms were designed pertinent to the objectives of the study.

Sources of Other Data
A. The patients` clinical history taken by Senior Attendant Registrar at patient admission to hospital. B. Direct registrar interview. C. Patients` interview. D. Laboratory results.

Preparation of data for statistical analysis
Raw data collection tools were retained and kept as original data records. Study logs were established and contained date of data receipt, investigation type, and data serial number. Data were entered to IBM SPSS software program base. Data cleaning was conducted including logic check, correction, and clarification.

Statistical analysis
Data were analyzed by means of One-way Analysis of Variants and Chen's D to compare the mean differences for various results. Differences were considered to be significant at P ≤ 0.05.

Demographic Characteristics of the Study Population
The majority of the participants were middleaged in both groups (98.6 and 86.4%); nonemployed (97.3 and 92.5%); with active lifestyle (91.9 and 89%); primary school educational level (36.5 and 28.1%); and residents to Kordofan (24.3 and 21.5). These results are shown in Table 1.

Fertilization
In 94.6 % of the study population pregnancy was spontaneous, see Fig. 1.

The Gravidity of Current Pregnancy
Almost half of the participants were primigravida. This is depicted in Fig. 2.

Eclamptic Diseases Classes
Based-on disease features, the types of gestational hypertension complications are shown in Fig. 4.

Clinical Features and the Types of Symptoms
Regarding the presenting symptoms, (47.8%) were asymptomatic. Symptomatic cases had symptoms' types presented in Fig. 5.

Clinical Laboratory Results
The mean serum calcium was decreased for normotensive pregnant women. The serum magnesium was increased among preeclamptic pregnant women comparable to the control group as shown in Table 2. The estimation of sample size using a computerized software and proper selection criteria has given valid evidence-based findings. This is shown in the normal statistic distribution of hypertensive and normotensive pregnant participants in the present investigation.

Table 2. Determinations of electrolytes including mean serum calcium and magnesium in patients of preeclampsia, and controls. The value of [Chen's D Calcium = 2.41], and [Chen's D
It has been determined that the majority of PIH patients (86.4%) were in age category of 18-40 years. This is justified by the fact that this is the age with high potential for conception in females at child-bearing age.
It has, presently, been determined that a large cohorts of controls, (24.3%) and of PIH patients, (21.5%), are from the rural area of Kurdofan; that most are illiterate, (17.1%); or primary school graduates, (28.1%); and that most are from low socio-economic background, (85.1%). These estimates can be attributed to low awareness about the early warning symptoms such as tachycardia, and oliguria. This is the consistent with ElFarra et. al. [29], who concluded that patients` awareness about the early warning symptoms can identify pregnant hypertensive women at high risk and allow timely diagnostic and therapeutic interventions. Moreover, studies have shown that up to 77 % of women affected with preeclampsia lack knowledge about preeclampsia, and therefore cannot take preventive measures [30].
Referral from rural areas of Kurdofan of PIH cases and normal control signals sacristy of maternity health care services and absence of the pregnancy follow up and antenatal visits rather than genetic predisposition to the disease, this in the line with the Shaker et. al. [31], who concluded that the frequency of antenatal care visits during pregnancy has a significant effect on maternal and fetal outcomes in patients with PIH. Additionally, the maternal inflammatory marker investigation which, currently, is not supported in Kurdofan rural areas may have affected the referral decision. Wright et. al. [32], reported that early maternal inflammatory marker investigation assessed the diagnosis of disease and early interventions. Prevalence of low socio-economic status among the present patients contributes to reluctancy to approach maternity care centers to avoid antenatal visits expenses, which contributes to poor outcomes. This is consistent with Wright et. al. [33], who studied the costeffectiveness in the management of preeclampsia complications.
The present study reveals that 20.7% of multigravida patients with PIH had previous history of preeclampsia. This can be taken as an evidence that the incidence of pregnancyinduced hypertension complications is heightened with progress of age and gravidity. This is logical although it contradicts an earlier report by Raymer et. al. [34].
It has been shown that multigravida with bad obstetrics history, (18.1%) are at increased risk for developing preeclampsia. The finding is consistent with a previous report of the risk factors associated with preeclampsia [35]. Neverthe-less, the finding that a previous history of miscarriage increases the risk of present miscarriage as a complication of preeclampsia agrees with earlier observations [36].
The present finding that half of the preeclamptic patients were primigravida, and the other half were multigravida, suggests the nature of the pathogenesis of the disease, and the response of maternal immunity to hemi-allogeneic placental cells, and that the co-expressing of maternal and paternal genomes in the same place contributes to the stimulation of maternal immunity. This is in the line with the findings of a previous report [37], that concluded that the immunological alterations were suggested to be a major etiology of placentation disease and therefore preeclampsia.
It has been estimated that the better half of patients in the current investigation, (52.2%), had a characteristic presentation of CNS or GIT symptoms and generalized edema. On the other hand, the second half (47.8% of patients) went naïve for routine follow up at antenatal care units and were referred to this specialized hospital for further care and investigations wherein the diagnosis of preeclampsia or other disease complications has been confirmed. These findings are consistent with an earlier report [38].
The present estimations of the significant differences in the serum calcium and magnesium between patients in one hand, and controls in the other, suggests that these divalent cations may play a role in the pathogenesis of preeclampsia. This is consistent with the estimations by previous investigators, [39], for serum calcium levels, and [40], for serum magnesium levels.

CONCLUSION
Status of pregnancy-induced hypertension and its complications among Sudanese women is determined. Maternal age between 18-40 years, nulliparous primigravida or multigravida with long latency period, and history of miscarriage are the commonest risk factors of hypertension complication during pregnancy, including preeclampsia, in Sudan; significantly lower serum calcium and/or higher serum magnesium are associated with preeclampsia; syndromic HELLP is a rare association. Patient awareness is critical for early detection and prevention of disease progression. We recommend dissemination of antenatal healthcare facilities in rural areas of the country to contribute to early detection, and prevention of poor natal outcomes.

DISCLAIMER
Authors have declared that no competing interests exist. The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

CONSENT
As per international standard or university standard, respondents' written consent has been collected and preserved by the author(s).

ETHICAL APPROVAL
The study proposal was approved by the Department Pharmacology, Faculty of Pharmacy, Omdurman Islamic University, Sudan. The ethical clearance for the research project has been issued by the Ethics Committee of the Ministry of Health, Khartoum State, Sudan. A final permission, prior to starting the study, has been obtained from the Head Consultant of Research Authorities and Ethical Committee at Omdurman Maternity Hospital.