An estimated 500,000 or more women die each year from complications of pregnancy and 95% of these women are in Africa and Asia [1]. Eclampsia is one of the leading causes of maternal mortality in Nigeria [2]. The World Health Organization (WHO) estimates that only 40% of birth in developing countries takes place in health facilities [3]. This is in tandem with 35% reported by Nigeria Demographic Health Survey in the year 2008 [4]. The opportunity to detect these women at the pre-eclamptic phase is usually lost. When care is sought, it is done late after a lot of delay and this contributes to maternal mortality. The collaborative eclamptic trials in 1995 conclusively proved that magnesium sulphate is the drug of choice for the anticonvulsant management of eclampsia rather than diazepam or phenytoin. The use of this drug reduced maternal deaths from 7% to 4% and the recurrence rate of convulsion was reduced by 52% and 67% when compared with diazepam, and phenytoin respectively. The use of magnesium sulphate has been shown to be effective in the treatment of eclampsia [5,6]. The two most widely used regimens of magnesium sulphate administration are the intramuscular (i.m) administration regimen popularized by Pritchard7 which is the preferred regimen in our study centre and the continuous intravenous (i.v) regimen recommended by Zuspan [7]. In the Pritchard regimen the loading dose of 4 g of magnesium sulphate is given intravenously slowly over 5-10 minutes and this is followed by 10 g given intramuscularly (5 g into each buttock). Subsequently, 5g is given intramuscularly into alternate buttock every 4 hours [5]. In the Zuspan regimen, the loading dose consist of an initial intravenous dose of 4 g slowly over 5-10 minutes followed by a maintenance dose of 1-2g every hour by an infusion pump [8]. Whatever regimen is chosen, the drug should be administered till 24 hours after delivery or after the last fit. The use of lower dosage of magnesium sulphate in the management of eclampsia is not new. The concept of using just the loading dose of magnesium sulphate to control and prevent fits in eclampsia was suggested by Boyd and Browse [9,10]. But the first comprehensive study was published in 2002 [11]. It was shown in that study that the recurrent convulsion rate was almost the same (3.96% versus 3.52%), between the group that had only a loading dose of 10 g (4 gram intravenous and 6 gram intramuscular) and the control group that had both the loading dose and the maintenance dose of 2.5 grams every four hours for 24 hours. However, the drug has remained largely unavailable in several developing countries where it is needed most. Even where it is available, the cost is the issue as most patients may not be able to afford this drug considering the level of poverty in low resource settings like ours. Low dose magnesium sulphate will reduce magnesium sulphate toxicity and need for serum level monitoring may not be necessary in resource constrained environment which will ultimately translate to reduced cost of treatment. This study aimed at evaluating the efficacy of low dose intravenous magnesium sulphate regimen compared with Pritchard intramuscular regimen being practiced in our study centre and assess feto-maternal outcome in both groups.

Study location

This study was conducted at the Obstetrics and Gynaecological Department of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria. The hospital comprises of two arms offering tertiary health care, the Ife Hospital Unit (IHU) in Ile- Ife and the Wesley Guild Hospital (WGH) in Ilesha, each with its own functioning Obstetrics and Gynaecology Unit. The Teaching Hospital serves as a tertiary referral centre for secondary and primary level healthcare providers within Ife-Ijesha, Ondo and Ekiti zones of the country, and with its two obstetrics units, the hospital records an average of 3,000 deliveries annually.

Study design

This was a randomized clinical trial.

Patients

All women with a clinical diagnosis of eclampsia were included in this trial. This was after the patient’s relatives have been verbally educated about the study and a written informed consent obtained by proxy from them.

Exclusion criteria

The patients with convulsion due to epilepsy or from other causes, known contraindication to magnesium sulphate therapy (like myasthenia gravis) and who had received any form of treatment from the referring hospital were excluded from the study.

Sample size determination

Kathleen Graham in her sub analysis of collaborative Eclamptic trial found that the rate of recurrent convulsion were 2.85% for Pritchard’s and 23.8% for Zuspan’s regimen.

n=28 patients per group approximately

A total of 56 patients are required to make the result statistically significant.

Study procedure

Upon completing the consent form, all the subjects’ baseline data were recorded in the study proforma for those that meet the criteria. Randomization was then done thereafter.

The primary measures of outcome were recurrence of convulsions, neonatal outcomes and maternal death. Secondary measures of outcome were potentially life-threatening events including pulmonary oedema, cardiac failure, respiratory depression, renal failure, postpartum haemorrhage,liver failure, and perinatal outcome.

Statistical analysis

Data obtained at end of the study were analysed using the computer software SPSS version 13. Frequency tables were made and results tested for significance using the student t-test for continuous variables and chi squared test for categorical variables with level of significance 5%.

Ethical consideration

Ethical clearance was obtained for this study from the research and ethics committee of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife. Confidentiality was also maintained as the patient identity was not revealed.

During the study period between July 2012 and January 2013 there were a total of 2,200 deliveries; out of these, 56 were eclamptic patients giving an overall incidence of 2.54%. The mean maternal age was 25.5 ± 5.7 years with range of 16 years to 40 years. The majority of the eclamptic women 34 (60.7%) were between the age of 20-29years while teenager constituted 8(14.3%). They were mainly nullipara 33(58.9%), unbooked were 54(96.4%). Seventeen (30.4%) had preterm delivery (Table 1).

Table 1: Maternal socio-demographic characteristics.

There were no statistically significant difference in age (25.32 years Vs. 25.57 years, p=0.872); parity (0.93 Vs 0.82, p=0.749), estimated gestational age at delivery (36.24 weeks Vs. 36.53 weeks, p=0.784); systolic blood pressure (171.43 mmHg Vs. 173.21 mmHg, p=0.798); diastolic blood pressure (109.64 mmHg Vs. 114.29 mmHg, p= 0.174); proteinuria (2.43+ Vs. 2.75+, p=0.125) and fit-treatment interval (5.52 hours Vs 7.90 hours, p= 0.367) across the treatment groups (Table 2).

Table 2: Clinical parameters across the treatment groups.

The patients were similar in terms of their booking status (i.v unbooked 96.4% Vs i.m. unbooked 96.4%, p=1.000); level of consciousness, (i.v. conscious, 55.3% Vs i.m. conscious 44.7 %, p=0.252); type of eclampsia, (i.v. antepartum 51.5% Vs i.m. antepartum 48.5%, p=0.956), and mode of delivery, (CS in i.v. group, 64.3% Vs 67.9% in i.m. group, p=0.949) across the treatment groups (Table 3).

Table 3: Neonatal outcome.

There was no statistically significant difference across the treatment groups, in terms of: recurrent convulsion, 7.1% Vs. 3.6% in i.v and i.m groups respectively (p=0.533), maternal death, 3.6% Vs. 3.6% in i.v. and i.m. groups respectively (p=1.000), left heart failure and pulmonary oedema, i.v 0.0% Vs i.m 3.6% (p= 0.313), post-partum haemorrhage i.v. 7.1% Vs i.m 0.0% groups respectively (p=0.150), renal failure, i.v 0% Vs i.m 3.6% (p=0.313), and disseminated intravascular coagulopathy, i.v. 3.6% Vs. i.m 0.0% groups (p=0.313) (Table 4).

Table 4: Maternal outcome in both groups.

There was also no statistically significant difference in birth weight (i.v. 2.64 kg Vs. i.m. 2.39 kg, p= 0.186), across the treatment groups (Table 3).

There was no statistically significant difference in stillbirth rate, (i.v 23.1% Vs. i.m 11.4% group, p=0.464), early neonatal death, (i.v 3.8% Vs. i.m 7.4% groups, p=0.464). From the medical record of this institution, the number of live birth during the study period was 2122. The stillbirth and early neonatal death were 138 and 36 respectively, while the perinatal mortality rate was 77/1000 (Table 5).

Table 5: Neonatal outcome.

In this study, the incidence of eclampsia of 2.54% is higher than what was previously reported in this institution [11,12]. This is probably because both studies were retrospective with possibility of loss of data as a result of poor record keeping and were also carried out in only in an arm of the hospital, while the present study is a prospective study which was carried out in both arms of the hospital. It is however similar to 2.45% reported in Eastern Nigeria but lower than figures from the Northern part of the country [13-16]. This is probably because of higher rate of teenage pregnancy which is a predisposing factor to this condition and possibly poor access to health facility [15].

The mean age of 25.5 ± 5.7 years in the present study is similar to findings from Lagos, Nigeria [17] but higher than reports from northern part of the country [18]. Most of the women in this study 33 (58.9%) were nullipara. This is in agreement with findings from other studies [12,18,19]. Majority of the women 54 (96.4%) in this study were unbooked. This is not surprising as lack of antenatal care is a risk factor for eclampsia. This was in agreement with findings from other parts of the country [18,20-22]. There were 17 (30.4%) preterm deliveries in this study corroborating other studies, which underscore the fact that the cure for eclampsia is stabilization and termination of the pregnancy [23].

Various anticonvulsants such diazepam, phenytoin, lytic cocktail have been used in the treatment and prevention of further fits [24-26]. But result of collaborative eclamptic trial has established magnesium sulphate as the gold standard in the management of eclampsia [27]. There are still a lot of unanswered questions about magnesium sulphate which include the minimum effective dose, the optimal protocol and duration of the maintenance [28]. There is also concern for the safety of magnesium sulphate because of its narrow therapeutic index. It is also costly and not readily available in developing countries like ours where most people live on less than $1 per day [29].

The recurrence of convulsion which is one of the prognostic factor in eclampsia is not significantly different in both groups. This ranged between 3.6% and 7.1% which is much lower than 27.9% for diazepam showings that magnesium sulphate is a better anticonvulsant than diazepam [13,27].

Eclampsia is associated with high maternal mortality. In this study there were 2 maternal deaths, one from each arm of the study.

The perinatal outcome in terms of birth weight, apgar score, stillbirth and perinatal mortality rate were similar in both treatment groups. The overall perinatal mortality rate reported for the study period was 77/1000. Eclampsia contributed 5.3/1000 to the perinatal mortality rate which is unacceptably high. This was similar to finding of Makinde in this institution [30,31].

The adverse maternal and perinatal outcome in this study is still unacceptably high due to poor antenatal care received by the patients; however, based on the findings from this study, consideration should be given to the use low dose Magnesium sulphate in the management of eclampsia as there are no significant difference between it and the standard Pritchard regime. The administration of low dose intravenous (19 g) magnesium sulphate appears to be as effective as (44 g) Pritchard intramuscular regimen in prevention of recurrent convulsion, adverse neonatal and maternal outcome. This will prevent magnesium sulphate toxicity, reduce the need for vigorous monitoring in the absence of facility to monitor serum magnesium level and magnesium sulphate will be available to treat more women. Using this regimen, the cost of treatment of eclampsia will be reduced by more than 50%.

Larger multi-centre randomized control trial is recommended to validate the outcome of this study.