Alternative magnesium sulphate regimens for women with pre-eclampsia and eclampsia.

BACKGROUND: Magnesium sulphate is the drug of choice for the prevention and treatment of women with eclampsia. Regimens for administration of this drug have evolved over the years, but there is no clarity on the comparative benefits or harm of alternative regimens. This is an update of a review first published in 2010. OBJECTIVES: To assess if one magnesium sulphate regimen is better than another when used for the care of women with pre-eclampsia or eclampsia, or both, to reduce the risk of severe morbidity and mortality for the woman and her baby. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (29 April 2022), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised trials and cluster-randomised trials comparing different regimens for administration of magnesium sulphate used in women with pre-eclampsia or eclampsia, or both. Comparisons included different dose regimens, intramuscular versus intravenous route for maintenance therapy, and different durations of therapy. We excluded studies with quasi-random or cross-over designs. We included abstracts of conference proceedings if compliant with the trustworthiness assessment. DATA COLLECTION AND ANALYSIS: For this update, two review authors assessed trials for inclusion, performed risk of bias assessment, and extracted data. We checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: For this update, a total of 16 trials (3020 women) met our inclusion criteria: four trials (409 women) compared regimens for women with eclampsia, and 12 trials (2611 women) compared regimens for women with pre-eclampsia. Most of the included trials had small sample sizes and were conducted in low- and middle-income countries. Eleven trials reported adequate randomisation and allocation concealment. Blinding of participants and clinicians was not possible in most trials. The included studies were for the most part at low risk of attrition and reporting bias. Treatment of women with eclampsia (four comparisons) One trial compared a loading dose-alone regimen with a loading dose plus maintenance dose regimen (80 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsions or maternal death (very low-certainty evidence). One trial compared a lower-dose regimen with standard-dose regimen over 24 hours (72 women). It is uncertain whether either regimen has an effect on the risk of recurrence of convulsion, severe morbidity, perinatal death, or maternal death (very low-certainty evidence). One trial (137 women) compared intravenous (IV) versus standard intramuscular (IM) maintenance regimen. It is uncertain whether either route has an effect on recurrence of convulsions, death of the baby before discharge (stillbirth and neonatal death), or maternal death (very low-certainty evidence). One trial (120 women) compared a short maintenance regimen with a standard (24 hours after birth) maintenance regimen. It is uncertain whether the duration of the maintenance regimen has an effect on recurrence of convulsions, severe morbidity, or side effects such as nausea and respiratory failure. A short maintenance regimen may reduce the risk of flushing when compared to a standard 24 hours maintenance regimen (risk ratio (RR) 0.27, 95% confidence interval (CI) 0.08 to 0.93; 1 trial, 120 women; low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials. Prevention of eclampsia for women with pre-eclampsia (five comparisons) Two trials (462 women) compared loading dose alone with loading dose plus maintenance therapy. Low-certainty evidence suggests an uncertain effect with either regimen on the risk of eclampsia (RR 2.00, 95% CI 0.61 to 6.54; 2 trials, 462 women) or perinatal death (RR 0.50, 95% CI 0.19 to 1.36; 2 trials, 462 women). One small trial (17 women) compared an IV versus IM maintenance regimen for 24 hours. It is uncertain whether IV or IM maintenance regimen has an effect on eclampsia or stillbirth (very low-certainty evidence). Four trials (1713 women) compared short postpartum maintenance regimens with continuing for 24 hours after birth. Low-certainty evidence suggests there may be a wide range of benefit or harm between groups regarding eclampsia (RR 1.99, 95% CI 0.18 to 21.87; 4 trials, 1713 women). Low-certainty evidence suggests there may be little or no effect on severe morbidity (RR 0.96, 95% CI 0.71 to 1.29; 2 trials, 1233 women) or side effects such as respiratory depression (RR 0.80, 95% CI 0.25 to 2.61; 2 trials, 1424 women). Three trials (185 women) compared a higher-dose maintenance regimen versus a lower-dose maintenance regimen. It is uncertain whether either regimen has an effect on eclampsia (very low-certainty evidence). Low-certainty evidence suggests that a higher-dose maintenance regimen has little or no effect on side effects when compared to a lower-dose regimen (RR 0.79, 95% CI 0.61 to 1.01; 1 trial 62 women). One trial (200 women) compared a maintenance regimen by continuous infusion versus a serial IV bolus regimen. It is uncertain whether the duration of the maintenance regimen has an effect on eclampsia, side effects, perinatal death, maternal death, or other neonatal morbidity (very low-certainty evidence). Many of our prespecified critical outcomes were not reported in the included trials. AUTHORS' CONCLUSIONS: Despite the number of trials evaluating various magnesium sulphate regimens for eclampsia prophylaxis and treatment, there is still no compelling evidence that one particular regimen is more effective than another. Well-designed randomised controlled trials are needed to answer this question.

Eclampsia: A Critical Pregnancy Complication Demanding Enhanced Maternal Care: A Review.

Eclampsia is the most serious pregnancy complication and one of the main causes of death of pregnant and delivering women. The mortality rate of young mothers is 5-20%, emphasizing the severity of this pregnancy-related disorder. Today many centers have only rare opportunities to see and deal with eclampsia cases; therefore, it is very important to bring this emergency medical condition to the attention of attending physicians. All patients with eclampsia, and after eclamptic seizures, should be treated in an intensive care unit. However, taking into account clinical realities, especially in developing countries, this is not always possible. It is necessary for all gynecologists-obstetricians to be fully prepared for eclampsia, although its occurrence is very rare. Drug treatment aims to stop eclampsia seizures and prevent reoccurrence of convulsions and complications. Magnesium sulphate is the drug of first choice used in treatment of eclampsia seizure, whereas treatment with the use of antihypertensive drugs and proper blood pressure control is one of the most important factors effectively reducing the risk of deaths or acute complications and poor pregnancy outcomes. The most urgent part of the treatment is the lifesaving procedure involving airways patency assessment, maintenance of breathing and blood circulation of the mother, securing an adequate oxygen level of the mother and thereby of the fetus, and prevention of injuries. This review aims to present an overview of the current prevalence, diagnosis, and management of eclampsia and the need for improved maternal care.

Optimizing Delivery Strategies in Eclampsia: A Comprehensive Review on Seizure Management and Birth Methods.

Eclampsia seizure is an always serious and potentially fatal obstetric condition. Safe delivery in women with pregnancies complicated by eclampsia seizures is still one of the greatest challenges in perinatal medicine. Pregnancy should be terminated (childbirth) in the safest and least traumatic way possible. Attempting vaginal delivery can take place only exceptionally, in the event of possibly quick completion of childbirth with a stable state of the mother and the fetus. However, immediate labor via cesarean section is most often recommended. It is essential to maintain left lateral patient positioning during cesarean section. Regional anesthesia can be used only in conscious patients who are free from coagulopathy and from HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome to decrease the risk of aspiration and failed intubation attempts in preeclamptic or eclamptic women. For sudden, unexpected interventions, when a patient arrives at the hospital with an eclampsia seizure without lab results, general anesthesia can be the best option and should be performed by an experienced medical team of anesthesiologists, ready to perform difficult intubation. Magnesium sulfate is the drug that should be used first to stop eclamptic convulsions and prevent their recurrence. Intravenous antihypertensive drugs can stabilize elevated blood pressure (BP), preventing multiorgan failure and recurrent eclampsia seizure, and thus the prevention of maternal death. This article aims to review the management of seizures during pregnancy in women with eclampsia to ensure safe delivery.

Factors affecting use of magnesium sulphate for pre-eclampsia or eclampsia: a qualitative evidence synthesis.

BACKGROUND: Hypertensive disorders account for 14% of global maternal deaths. Magnesium sulphate (MgSO4 ) is recommended for prevention and treatment of pre-eclampsia/eclampsia. However, MgSO4 remains underused, particularly in low- and middle-income countries (LMICs). OBJECTIVE: This qualitative evidence synthesis explores perceptions and experiences of healthcare providers, administrators and policy-makers regarding factors affecting use of MgSO4 to prevent or treat pre-eclampsia/eclampsia. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Emcare, CINAHL, Global Health and Global Index Medicus, and grey literature for studies published between January 1995 and June 2021. SELECTION CRITERIA: Primary qualitative and mixed-methods studies on factors affecting use of MgSO4 in healthcare settings, from the perspectives of healthcare providers, administrators and policy-makers, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We applied a thematic synthesis approach to analysis, using COM-B behaviour change theory to map factors affecting appropriate use of MgSO4 . MAIN RESULTS: We included 22 studies, predominantly from LMICs. Key themes included provider competence and confidence administering MgSO4 (attitudes and beliefs, complexities of administering, knowledge and experience), capability of health systems to ensure MgSO4 availability at point of use (availability, resourcing and pathways to care) and knowledge translation (dissemination of research and recommendations). Within each COM-B domain, we mapped facilitators and barriers to physical and psychological capability, physical and social opportunity, and how the interplay between these domains influences motivation. CONCLUSIONS: These findings can inform policy and guideline development and improve implementation of MgSO4 in clinical care. Such action is needed to ensure this life-saving treatment is widely available and appropriately used. TWEETABLE ABSTRACT: Global qualitative review identifies factors affecting underutilisation of MgSO4 for pre-eclampsia and eclampsia.

Neonatal magnesium levels are safe after maternal MgSO4 administration: a comparison between unexposed preterm neonates and neonates exposed for fetal neuroprotection or maternal eclampsia prevention-a cohort study.

To objective of this study was to compare neonatal magnesemia in the first 15 days of neonatal life between three groups: a control group not exposed to MgSO4, a neuroprotection group, and an eclampsia prevention group, and to explore its associations with child outcomes. A retrospective single-centre cohort study was performed in a tertiary care setting. Infants admitted at the neonatal intensive care unit born between 24 and 32 weeks' gestation, regardless of etiology of preterm birth, were included. The mean outcome measure was neonatal magnesemia (mmol/L). Linear mixed regression of neonatal magnesemia on exposure group and day of life was done. Generalised estimating equation models of child outcomes on neonatal magnesemia according to exposure group and day of life were made. The analyses showed that in neonatal magnesemia is significantly higher in the preeclampsia group compared to the control and neuroprotection groups. On the day of birth, this is irrespective of maternal magnesemia (preeclampsia vs control groups), and the maternal total dose or duration of MgSO4 administration (preeclampsia vs neuroprotection group). No differences were found in short-term composite outcome between the three groups. CONCLUSION: We found mean differences in neonatal magnesemia between children not exposed to MgSO4 antenatally, children exposed for fetal neuroprotection, and children exposed for maternal eclampsia prevention. A 4-g loading and 1-g/h maintenance doses, for fetal neuroprotection and eclampsia prevention, appear to be safe on the short term for the neonate. WHAT IS KNOWN: • Magnesium sulphate is a valuable medicine in obstetrics. The main indications are prevention of eclampsia and fetal neuroprotection. The most used dosage is a 4- or 6-g loading dose and a 1- or 2-g per h maintenance dose. It reduces neuromotor disabilities in extreme-to-moderate preterm born children. WHAT IS NEW: • Maternal concentrations are supraphysiological and the maternal total dose can be high. Concentrations in neonates appear to remain in safe ranges. A dosage of 4-g loading and 1 g/h seems safe for the preterm neonate on the short term.

The WHO Safe Childbirth Checklist implementation: impact on the prescription of magnesium sulphate through a one-year longitudinal study.

BACKGROUND: Preeclampsia is a relatively frequent condition during pregnancy and childbirth. The administration of magnesium sulphate as a prophylactic and treatment measure is an evidence-based practice for eclampsia; however, it is not consistently used, compromising the health of pregnant women. This study aimed to assess compliance with recommendations of the International Society for the Study of Hypertension in Pregnancy (ISSHP) for the use of MgSO4 in pregnant women with preeclampsia, before and after the implementation of the World Health Organization Safe Childbirth Checklist (SCC). METHODS: This quasi-experimental study was conducted between July 2015 and July 2016 at a third-level maternity hospital in northeastern Brazil, where the SCC was implemented. Compliance (underuse and overuse of MgSO4) was assessed in biweekly samples of 30 deliveries assessed 6 months before and 6 months after SCC implementation, using indicators based on international guidelines. A total of 720 deliveries were assessed over 1 year using an ad hoc application for reviewing medical records. Aggregated adequate use was estimated for the study period, and the time series measurements were compared to a control chart to assess change. RESULTS: The incidence of preeclampsia was 39.9% (287/720). Among these, 64.8% (186/287) had severe signs or symptoms and needed MgSO4. Underuse (no prescription when needed) of MgSO4 was observed in 74.7% (139/186) of women who needed the drug. Considering all women, non-compliance with the prescription protocol (underuse and overuse) was 20.0% (144/720). After introducing the SCC, the use of MgSO4 in women with preeclampsia with severe features increased from 19.1 to 34.2% (p = 0.025). Longitudinal analysis showed a significant (p < 0.05) ascending curve of adequate use of MgSO4 after the SCC was implemented. CONCLUSIONS: Compliance with recommendations for the use of MgSO4 in preeclampsia was low, but improved after implementation of the SCC. Interventions to improve compliance based on diagnosis and treatment reminders may help in the implementation of this good practice.

Knowledge of pharmacy workers on antihypertensive and anticonvulsant drugs for managing pre-eclampsia and eclampsia in Bangladesh.

BACKGROUND: Pharmacy workers in Bangladesh play an important role in managing pregnancy complications by dispensing, counselling and selling drugs to pregnant women and their families. This study examined pharmacy workers' drug knowledge and practice for pre-eclampsia and eclampsia (PE/E) management, including antihypertensives and anticonvulsants, and determine factors associated with their knowledge. METHODS: A cross-sectional survey with 382 pharmacy workers in public facilities (government) and private pharmacies and drug stores assessed their knowledge of antihypertensive and anticonvulsant drugs. 'Pharmacy workers' include personnel who work at pharmacies, pharmacists, family welfare visitors (FWVs), sub-assistant community medical officers (SACMOs), drug storekeepers. Exploratory and multivariate logistic models were used to describe association between knowledge of medicines used in pregnancy and demographic characteristics of pharmacy workers. RESULTS: Overall, 53% pharmacy workers interviewed were drug store owners in private pharmacies while 27% FWVs/SACMOs, who are government service providers also work as drug prescribers and/or dispensers in public facility pharmacies. Majority of pharmacy workers had poor knowledge compared to correct knowledge on both antihypertensive (77.8% vs 22.3%; p < 0.001) and anticonvulsant drugs (MgSO4) (82.2% vs 17.8%; p < 0.001). Multivariate analysis showed SACMOs and FWVs were greater than 4 times more likely to have correct knowledge on anti-hypertensives (AOR = 4.2, 95% CI:1.3-12.3, P < 0.01) and anticonvulsant drugs (AOR = 4.9, 95% CI:1.3-18.1, P < 0.01) compared to pharmacists. Pharmacy workers who had received training were more likely to have correct knowledge on antihypertensive and anticonvulsant drugs than those who had no training. CONCLUSIONS: Pharmacy workers' knowledge and understanding of antihypertensive and anticonvulsant drugs, particularly for prevention and management of PE/E is limited in Bangladesh. Most pharmacies surveyed are private and staffed with unskilled workers with no formal training on drugs. Expansion of maternal and newborn health programs should consider providing additional skills training to pharmacy workers, as well as regulating these medicines at informal pharmacies to mitigate any harmful practices or adverse outcomes of unauthorized and incorrectly prescribed and used drugs. It is important that correct messaging and medicines are available as drug stores are often the first point of contact for most of the women and their families.

A primary health care model for managing pre-eclampsia and eclampsia in low- and middle- income countries.

BACKGROUND: Hypertensive disorders in pregnancy, specifically pre-eclampsia and eclampsia (PE/E), are the second biggest killer of pregnant women globally and remains the least understood and most challenging maternal morbidity to manage. Although great strides were made in reducing maternal and newborn mortality between 1990 and 2015, this was clearly not enough to achieve the global health goals. To reduce maternal deaths: 1) early detection of PE needs to be improved; 2) effective management of PE/E needs to occur at lower health system levels and should encourage timely care-seeking; and 3) prioritizing the scale up of a comprehensive package of services near to where women live. FINDINGS: This commentary describes a pragmatic approach to test scalable and sustainable strategies for expanding access to quality under-utilized maternal health commodities, interventions and services. We present a primary health care (PHC) PE/E Model based on implementation research on identified gaps in care in several countries, accepted global best practice and built on the basic premise that PHC providers can take on additional skills with adequate capacity building, coaching and supervision, and community members desire control over their own health. The PHC PE/E model displays the linkages and opportunities to prevent and treat PE/E in a simplified way; however, there are numerous interlinking factors, angles, and critical points to consider including leadership, policies and protocols; relevant medicines and commodities, ongoing capacity building strategies at lower levels and understanding what women and their communities want for safe pregnancies. CONCLUSION: The PHC model described here uses PE/E as an entry to improve the quality of ANC and by extension the pregnancy continuum. Bringing preventive and treatment services nearer to where pregnant women live makes sense.

Antepartum eclampsia with reversible cerebral vasoconstriction and posterior reversible encephalopathy syndromes.

A 39-year-old pregnant woman was experienced thunderclap headache due to reversible cerebral vasoconstriction syndrome (RCVS) as a prodromal symptom. Two days after, she was brought to our hospital after an eclamptic seizure at 35 weeks of gestation. After management with magnesium sulphate, a cesarean delivery was performed, and passed without eclamptic seizure recurrence with calcium channel blocker (CCB) administration for hypertension and prophylaxis of another seizure. Antepartum eclampsia is sometimes complicated by headache as a prodromal symptom. Cerebrovascular diseases in the perinatal period include eclampsia, RCVS and posterior reversible encephalopathy syndrome, which have potentially overlapping pathologies. Here, we first report a case of overlapping those three diseases in the antepartum period. Our best literature review showed that antepartum RCVS is severe and has complications besides thunderclap headache, and there is a case report which CCB administration was shown to be effective in the treatment of antepartum RCVS. If thunderclap headache is recognized, prediction of eclampsia and getting better course of RCVS with CCB administration may be possible.

Eclampsia in Australia and New Zealand: A prospective population-based study.

BACKGROUND: Eclampsia is a serious consequence of pre-eclampsia. There are limited data from Australia and New Zealand (ANZ) on eclampsia. AIM: To determine the incidence, management and perinatal outcomes of women with eclampsia in ANZ. MATERIALS AND METHODS: A two-year population-based descriptive study, using the Australasian Maternity Outcomes Surveillance System (AMOSS), carried out in 263 sites in Australia, and all 24 New Zealand maternity units, during a staggered implementation over 2010-2011. Eclampsia was defined as one or more seizures during pregnancy or postpartum (up to 14 days) in any woman with clinical evidence of pre-eclampsia. RESULTS: Of 136 women with eclampsia, 111 (83%) were in Australia and 25 (17%) in New Zealand. The estimated incidence of eclampsia was 2.2 (95% confidence interval (CI) 1.9-2.7) per 10 000 women giving birth. Aboriginal and Torres Strait Islander women were over-represented in Australia (n = 9; 8.1%). Women with antepartum eclampsia (n = 58, 42.6%) were more likely to have a preterm birth (P = 0.04). Sixty-three (47.4%) women had pre-eclampsia diagnosed prior to their first eclamptic seizure of whom 19 (30.2%) received magnesium sulphate prior to the first seizure. Nearly all women (n = 128; 95.5%) received magnesium sulphate post-seizure. No woman received prophylactic aspirin during pregnancy. Five women had a cerebrovascular haemorrhage, and there were five known perinatal deaths. CONCLUSIONS: Eclampsia is an uncommon consequence of pre-eclampsia in ANZ. There is scope to reduce the incidence of this condition, associated with often catastrophic morbidity, through the use of low-dose aspirin and magnesium sulphate in women at higher risk.

Antenatal magnesium sulphate and adverse neonatal outcomes: A systematic review and meta-analysis.

BACKGROUND: There is widespread, increasing use of magnesium sulphate in obstetric practice for pre-eclampsia, eclampsia, and preterm fetal neuroprotection; benefit for preventing preterm labour and birth (tocolysis) is unproven. We conducted a systematic review and meta-analysis to assess whether antenatal magnesium sulphate is associated with unintended adverse neonatal outcomes. METHODS AND FINDINGS: CINAHL, Cochrane Library, LILACS, MEDLINE, Embase, TOXLINE, and Web of Science, were searched (inceptions to 3 September 2019). Randomised, quasi-randomised, and non-randomised trials, cohort and case-control studies, and case reports assessing antenatal magnesium sulphate for pre-eclampsia, eclampsia, fetal neuroprotection, or tocolysis, compared with placebo/no treatment or a different magnesium sulphate regimen, were included. The primary outcome was perinatal death. Secondary outcomes included pre-specified and non-pre-specified adverse neonatal outcomes. Two reviewers screened 5,890 articles, extracted data, and assessed risk of bias following Cochrane Handbook and RTI Item Bank guidance. For randomised trials, pooled risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs), were calculated using fixed- or random-effects meta-analysis. Non-randomised data were tabulated and narratively summarised. We included 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19,265 women and their babies) were conducted from 1987 to 2018 across high- (16 trials) and low/middle-income countries (23 trials) (1 mixed). Indications included pre-eclampsia/eclampsia (24 trials), fetal neuroprotection (7 trials), and tocolysis (9 trials); 18 trials compared magnesium sulphate with placebo/no treatment, and 22 compared different regimens. For perinatal death, no clear difference in randomised trials was observed between magnesium sulphate and placebo/no treatment (RR 1.01; 95% CI 0.92 to 1.10; 8 trials, 13,654 babies), nor between regimens. Eleven of 138 non-randomised studies reported on perinatal death. Only 1 cohort (127 babies; moderate to high risk of bias) observed an increased risk of perinatal death with >48 versus ≤48 grams magnesium sulphate exposure for tocolysis. No clear secondary adverse neonatal outcomes were observed in randomised trials, and a very limited number of possible adverse outcomes warranting further consideration were identified in non-randomised studies. Where non-randomised studies observed possible harms, often no or few confounders were controlled for (moderate to high risk of bias), samples were small (200 babies or fewer), and/or results were from subgroup analyses. Limitations include missing data for important outcomes across most studies, heterogeneity of included studies, and inclusion of published data only. CONCLUSIONS: Our findings do not support clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes. Further large, high-quality studies (prospective cohorts or individual participant data meta-analyses) assessing specific outcomes, or the impact of regimen, pregnancy, or birth characteristics on these outcomes, would further inform safety recommendations. PROSPERO: CRD42013004451.

Quality of care in early detection and management of pre-eclampsia/eclampsia in health facilities in Afghanistan.

BACKGROUND: Afghanistan faces a high burden of maternal and neonatal morbidity and mortality. Hypertensive disorders of pregnancy, including pre-eclampsia and eclampsia (PE/E), are among the most common causes of maternal and neonatal complications. Hypertensive disorders of pregnancy can lead to fatal complications for both the mother and fetus. The 2016 Afghanistan National Maternal and Newborn Health Quality of Care Assessment assessed quality of early detection and management of PE/E in health facilities and skilled birth attendants' (SBAs) perceptions of their working environment. METHODS: All accessible public health facilities with an average of at least five births per day (n = 77), a nationally representative sample of public health facilities with less than five births per day (n = 149), and 20 purposively selected private health facilities were assessed. Methods included a facility inventory and record review, interviews with SBAs, and direct clinical observation of antenatal care (ANC), intrapartum care and immediate postnatal care (PNC), as well as severe PE/E case management. RESULTS: Most facilities had supplies and medicines for early detection and management of PE/E. At public health facilities, 357 of 414 (86.2%) clients observed during ANC consultations had their blood pressure checked and 159 (38.4%) were asked if they had experienced symptoms of PE/E. Only 553 of 734 (72.6%) SBAs interviewed were able to correctly identify severe pre-eclampsia described in a case scenario. Of 29 PE/E cases observed, 17 women (59%) received the correct loading dose of magnesium sulfate (MgSO4) and 12 women (41%) received the correct maintenance dose of MgSO4. At private health facilities, 39 of 45 ANC clients had their blood pressure checked and 9 of 45 (20%) were asked about symptoms of PE/E. Fifty-four of 64(84.4%) SBAs in private facilities correctly identified severe pre-eclampsia described in a case scenario. CONCLUSION: Notable gaps in SBAs' knowledge and clinical practices in detection and management of PE/E in various health facilities increase the risk of maternal and perinatal mortality. Continuing education of health care providers and increased investment in focused quality improvement initiatives will be critical to improve the quality of health care services in Afghanistan.

Sequential occurrence of eclampsia-associated posterior reversible encephalopathy syndrome and reversible splenial lesion syndrome (a case report): proposal of a novel pathogenesis for reversible splenial lesion syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare clinic-radiological entity characterized by headache, an altered mental status, visual disturbances, and seizures. Reversible splenial lesion syndrome (RESLES) is a new clinic-radiological syndrome characterized by the presence of reversible lesions with transiently restricted diffusion (cytotoxic edema) in the splenium of the corpus callosum (SCC) on magnetic resonance (MR) images. Here we report a rare case involving a 23-year-old pregnant woman with eclampsia who sequentially developed PRES and RESLES. CASE PRESENTATION: The patient, a 23-year-old pregnant woman, presented with sudden-onset headache, dizziness, and severe hypertension (blood pressure, 170/110 mmHg). Brain MR imaging (MRI) revealed T2 hyperintense lesions in the posterior circulation territories. Immediate cesarean section was performed, and the patient received intravenous infusion of mannitol (125 ml, q8h) for 8 days for the treatment of PRES. Ten days later, or 1 day after the discontinuation of mannitol, T2-weighted MRI showed that the hyperintense lesions (vasogenic edema) had disappeared. However, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping revealed an isolated lesion in the splenium of the corpus callosum (SCC) that was accompanied by restricted diffusion (cytotoxic edema); these findings indicated reversible splenial lesion syndrome (RESLES). Five days after the discontinuation of mannitol, she had no abnormal symptoms and was discharged from our hospital. Brain MRI performed 29 days after the clinical onset of symptoms showed no abnormalities. CONCLUSION: The sequential occurrence of the two reversible diseases in our patient prompted us to propose a novel pathogenesis for RESLES. Specifically, we believe that the vasogenic edema in PRES was reduced with mannitol treatment, which increased the hyperosmotic stress and opened the blood-brain barrier; meanwhile, upregulation of aquaporin-4 expression secondary to the increased osmotic pressure resulted in cytotoxic edema in the astrocytes in SCC (RESLES). Further research is necessary to confirm this possible pathogenesis.

Screening and management of pre-eclampsia and eclampsia in antenatal and labor and delivery services: findings from cross-sectional observation studies in six sub-Saharan African countries.

BACKGROUND: Preeclampsia and eclampsia (PE/E) are major contributors to maternal and neonatal deaths in developing countries, associated with 10-15% of direct maternal deaths and nearly a quarter of stillbirths and newborn deaths, many of which are preventable with improved care. We present results related to WHO-recommended interventions for screening and management of PE/E during antenatal care (ANC) and labor and delivery (L & D) from a study conducted in six sub-Saharan African countries. METHODS: From 2010 to 2012, cross-sectional studies which directly observed provision of ANC and L & D services in six sub-Saharan African countries were conducted. Results from 643 health facilities of different levels in Ethiopia (n = 19), Kenya (n = 509), Madagascar (n = 36), Mozambique (n = 46), Rwanda (n = 72), and Tanzania (n = 52), were combined for this analysis. While studies were sampled separately in each country, all used standardized observation checklists and inventory assessment tools. RESULTS: 2920 women receiving ANC and 2689 women in L & D were observed. Thirty-nine percent of ANC clients were asked about PE/E danger signs, and 68% had their blood pressure (BP) taken correctly (range 48-96%). Roughly half (46%) underwent testing for proteinuria. Twenty-three percent of women in L & D were asked about PE/E danger signs (range 11-34%); 77% had their BP checked upon admission (range 59-85%); and 6% had testing for proteinuria. Twenty-five cases of severe PE/E were observed: magnesium sulfate (MgSO4) was used in 15, not used in 5, and for 5 use was unknown. The availability of MgSO4 in L & D varied from 16% in Ethiopia to 100% in Mozambique. CONCLUSIONS: Observed ANC consultations and L & D cases showed low use of WHO-recommended practices for PE/E screening and management. Availability of MgSO4 was low in multiple countries, though it was on the essential drug list of all surveyed countries. Country programs are encouraged to address gaps in screening and management of PE/E in ANC and L & D to contribute to lower maternal and perinatal mortality.

Availability and use of magnesium sulphate at health care facilities in two selected districts of North Karnataka, India.

BACKGROUND: Pre-eclampsia and eclampsia are major causes of maternal morbidity and mortality. Magnesium sulphate is accepted as the anticonvulsant of choice in these conditions and is present on the WHO essential medicines list and the Indian National List of Essential Medicines, 2015. Despite this, magnesium sulphate is not widely used in India for pre-eclampsia and eclampsia. In addition to other factors, lack of availability may be a reason for sub-optimal usage. This study was undertaken to assess the availability and use of magnesium sulphate at public and private health care facilities in two districts of North Karnataka, India. METHODS: A facility assessment survey was undertaken as part of the Community Level Interventions for Pre-eclampsia (CLIP) Feasibility Study which was undertaken prior to the CLIP Trials (NCT01911494). This study was undertaken in 12 areas of Belagavi and Bagalkote districts of North Karnataka, India and included a survey of 88 facilities. Data were collected in all facilities by interviewing the health care providers and analysed using Excel. RESULTS: Of the 88 facilities, 28 were public, and 60 were private. In the public facilities, magnesium sulphate was available in six out of 10 Primary Health Centres (60%), in all eight taluka (sub-district) hospitals (100%), five of eight community health centres (63%) and both district hospitals (100%). Fifty-five of 60 private facilities (92%) reported availability of magnesium sulphate. Stock outs were reported in six facilities in the preceding six months - five public and one private. Twenty-five percent weight/volume and 50% weight/volume concentration formulations were available variably across the public and private facilities. Sixty-eight facilities (77%) used the drug for severe pre-eclampsia and 12 facilities (13.6%) did not use the drug even for eclampsia. Varied dosing schedules were reported from facility to facility. CONCLUSIONS: Poor availability of magnesium sulphate was identified in many facilities, and stock outs in some. Individual differences in usage were identified. Ensuring a reliable supply of magnesium sulphate, standard formulations and recommendations of dosage schedules and training may help improve use; and decrease morbidity and mortality due to pre-eclampsia/ eclampsia. TRIAL REGISTRATION: The CLIP trial was registered with ClinicalTrials.gov ( NCT01911494 ).

Clinical practice patterns on the use of magnesium sulphate for treatment of pre-eclampsia and eclampsia: a multi-country survey.

OBJECTIVE: To characterise the current clinical practice patterns regarding the use of magnesium sulphate (MgSO4 ) for eclampsia prevention and treatment in a multi-country network of health facilities and compare with international recommendations. DESIGN: Cross-sectional survey. SETTING: A total of 147 health facilities in 15 countries across Africa, Latin America and Asia. POPULATION: Heads of obstetric departments or maternity units. METHODS: Anonymous online and paper-based survey conducted in 2015. MAIN OUTCOME MEASURES: Availability and use of MgSO4 ; availability of a formal clinical protocol for MgSO4 administration; and MgSO4 dosing regimens for eclampsia prevention and treatment. RESULTS: Magnesium sulphate and a formal protocol for its administration were reported to be always available in 87.4% and 86.4% of all facilities, respectively. MgSO4 was used for the treatment of mild pre-eclampsia, severe pre-eclampsia and eclampsia in 24.3%, 93.5% and 96.4% of all facilities, respectively. Regarding the treatment of severe pre-eclampsia, 26.4% and 7.0% of all facilities reported using dosing regimens that were consistent with Zuspan and Pritchard regimens, respectively. Across regions, intramuscular maintenance regimens were more commonly used in the African region (45.7%) than in the Latin American (3.0%) and Asian (22.9%) regions, whereas intravenous maintenance regimens were more often used in the Latin American (94.0%) and Asian (60.0%) regions than in the African region (21.7%). Similar patterns were found for the treatment of eclampsia across regions. CONCLUSIONS: The reported clinical use of MgSO4 for eclampsia prevention and treatment varied widely, and was largely inconsistent with current international recommendations. TWEETABLE ABSTRACT: MgSO4 regimens for eclampsia prevention and treatment in many hospitals are inconsistent with international recommendations.

Safety and efficacy of low dose intramuscular magnesium sulphate (MgSO4) compared to intravenous regimen for treatment of eclampsia.

AIM: This study was performed to compare the safety and efficacy of low dose intramuscular magnesium sulphate (MgSO4) (Dhaka regimen) and intravenous (IV) MgSO4 (Zuspan regimen) for the prevention of eclampsia recurrence and to compare serum magnesium concentration. METHODS: Forty one eligible patients with eclampsia were randomly divided into two groups: group I patients received IV MgSO4 according to the Zuspan regime, while group II patients received intramuscular (IM) MgSO4 according to the Dhaka regimen (i.e. low dose MgSO4). The total dose MgSo4 requirements per patient were calculated and serum MgSo4 level was measured. Maternal and fetal outcomes were compared between the groups. RESULTS: The mean total dose of MgSO4 required for the treatment of eclampsia was higher in group I compared to group II (32 ± 6.8 g vs 25.4 ± 8.8 g, respectively; P < 0.5). The mean serum MgSO4 levels were significantly higher (P < 0.003) in group I compared to group II, although there were no significant differences in seizure recurrence. Statistically, more patients in group I experienced a loss of knee jerk reaction and required dose deferral compared to group II. There was a significantly higher number of babies with poor Apgar scores in group I. Overall the maternal and fetal outcomes were comparable between the groups. CONCLUSIONS: A low dose IM regimen (Dhaka regimen) of MgSo4 is equally efficacious and safe compared to an IV regimen (Zuspan regimen) for the control and prevention of seizures in patients with eclampsia.

Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia.

BACKGROUND: The pharmacokinetic basis of magnesium sulphate (MgSO4 ) dosing regimens for eclampsia prophylaxis and treatment is not clearly established. OBJECTIVES: To review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre-eclampsia and/or eclampsia. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies. SELECTION CRITERIA: All study types investigating pharmacokinetic properties of MgSO4 in women with pre-eclampsia and/or eclampsia. DATA COLLECTION AND ANALYSIS: Two authors extracted data on basic pharmacokinetic parameters reflecting the different aspects of absorption, bioavailability, distribution and excretion of MgSO4 according to identified dosing regimens. MAIN RESULTS: Twenty-eight studies investigating pharmacokinetic properties of 17 MgSO4 regimens met our inclusion criteria. Most women (91.5%) in the studies had pre-eclampsia. Baseline serum magnesium concentrations were consistently <1 mmol/l across studies. Intravenous loading dose between 4 and 6 g was associated with a doubling of this baseline concentration half an hour after injection. Maintenance infusion of 1 g/hour consistently produced concentrations well below 2 mmol/l, whereas maintenance infusion at 2 g/hour and the Pritchard intramuscular regimen had higher but inconsistent probability of producing concentrations between 2 and 3 mmol/l. Volume of distribution of magnesium varied (13.65-49.00 l) but the plasma clearance was fairly similar (4.28-5.00 l/hour) across populations. CONCLUSION: The profiles of Zuspan and Pritchard regimens indicate that the minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted level. Exposure-response studies to identify effective alternative dosing regimens should target concentrations achievable by these standard regimens. TWEETABLE ABSTRACT: Minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted therapeutic level.

Alternative regimens of magnesium sulfate for treatment of preeclampsia and eclampsia: a systematic review of non-randomized studies.

INTRODUCTION: The optimal dosing regimen of magnesium sulfate for treating preeclampsia and eclampsia is unclear. Evidence from the Cochrane review of randomized controlled trials (RCTs) was inconclusive due to lack of relevant data. MATERIAL AND METHODS: To complement the evidence from the Cochrane review, we assessed available data from non-randomized studies on the comparative efficacy and safety of alternative magnesium sulfate regimens for the management of preeclampsia and eclampsia. Sources included Medline, EMBASE, Popline, CINAHL, Global Health Library, African Index Medicus, Biological abstract, BIOSIS and reference lists of eligible studies. We selected non-randomized study designs including quasi-RCTs, cohort, case-control and cross-sectional studies that compared magnesium sulfate regimens in women with preeclampsia or eclampsia. RESULTS: Of 6178 citations identified, 248 were reviewed in full text and five studies of low to very low quality were included. Compared with standard regimens, lower-dose regimens appeared equally as good in terms of preventing seizures [odds ratio (OR) 1.02, 95% confidence interval (CI) 0.46-2.28, 899 women, four studies], maternal morbidity (OR 0.47, 95%CI 0.32-0.71, 796 women, three studies), and fetal and/or neonatal mortality (OR 0.87, 95%CI 0.38-2.00, 800 women, four studies). Comparison of loading dose only with maintenance dose regimens showed no differences in seizure rates (OR 0.99, 95%CI 0.22-4.50, 146 women, two studies), maternal morbidity (OR 0.53, 95%CI 0.15-1.93, 146 women, two studies), maternal mortality (OR 0.63, 95%CI 0.05-7.50, 146 women, two studies), and fetal and/or neonatal mortality (OR 0.49, 95%CI 0.23-1.03, 146 women, two studies). CONCLUSION: Lower-dose and loading dose-only regimens could be as safe and efficacious as standard regimens; however, this evidence comes from low to very low quality studies and further high quality studies are needed.