Pre-eclampsia in low and middle income countries

doi:10.1016/j.bpobgyn.2011.04.002

Best Practice & Research Clinical Obstetrics & Gynaecology

Volume 25, Issue 4, August 2011, Pages 537-548

https://doi.org/10.1016/j.bpobgyn.2011.04.002 Get rights and content

Pre-eclampsia and eclampsia are leading causes of maternal and perinatal morbidity and mortality worldwide. The exact prevalence, however, is unknown. The majority of pre-eclampsia related deaths in LMIC occur in the community and therefore, interventions must be focused at this level. There are a number of unique challenges facing LMIC but the principles of care for women with pre-eclampsia remain the same as in well resourced settings.

Three primary delays lead to an increased incidence of maternal mortality from pre-eclampsia- delays in triage, transport and treatment. There are a number of other challenges facing LMIC and the health care worker shortage is particularly significant. Task shifting is a potential strategy to address this challenge. Community health care workers, specifically lady health care workers, are an integral part of the health care force in many LMIC and can be employed to provide timely care to women with pre-eclampsia.

Prevention strategies should be applied to every pregnant woman since we cannot predict who will develop pre-eclampsia given the limitation in resources. Aspirin and calcium are the only two recommended therapies at this time. Measuring blood pressure and proteinuria is challenging in LMIC due to financial cost and lack of training. A detection tool that is affordable and can be easily applied is needed. Magnesium sulfate is the drug of choice for the prevention and treatment of eclampsia but it is underutilized due to barriers on multiple levels.

Section snippets

Definition of LMIC

There are 144 LMIC according to the World Bank classification of countries.⁶ Countries are categorized according to income based on the 2009 Gross National Income (GNI) per capita.⁶ The groups are: low income, $995 or less; lower middle income, $996–$3,945; upper middle income, $3,946–$12,195; and high income, $12,196 or more.⁶ There are 40 low income countries, 56 lower middle income countries and 48 upper middle income countries.

Epidemiology of pre-eclampsia in LMIC

Worldwide, pre-eclampsia is the second leading cause of direct

Overview of challenges in LMIC

The Safe Motherhood Initiative, launched in 1987 and targeted towards improving emergency obstetric care, has made access to high quality obstetric care throughout pregnancy and immediately after childbirth, one of its priorities.¹² Despite this, the absence of pre-conception care coupled with a lack of effective and universal antenatal care remains a serious challenge in LMIC. Many women with pre-eclampsia, particularly, at the community level are missed due to the lack of antenatal care.

The role of task shifting

Given the shortages of the health workface and skill-mix imbalances, task shifting may be a promising strategy. Task shifting is defined as delegating tasks to existing or new personnel with either less training or narrowly tailored training.¹⁹ The primary objective of task shifting is to increase productivity and efficiency by increasing the number of health care services provided at a given quality and cost, or alternatively, to provide the same level of health care services at a given

Prevention of pre-eclampsia

High resource settings have the capability of identifying women at risk (adequate antenatal care and through biomarkers and uterine artery dopplers) and, therefore, applying prevention strategies. In LMIC, prevention strategies should be applied to every pregnant woman since predicting which women will develop the condition is not feasible with current resources. There are only two recommended therapies for the prevention of pre-eclampsia currently: aspirin and calcium.

Detection of pre-eclampsia

Pre-eclampsia is classically defined by its most common features: hypertension and proteinuria. The new 2001 WHO antepartum care model calls for blood pressure check in the second antenatal visit in addition to testing for proteinuria but only in nulliparous women or in women with previous pre-eclampsia.³² However, there are fundamental challenges inherent to this practice in low-resource settings. For example, significant training is needed to accurately measure blood pressure, along with

Antihypertensives

Once a woman is diagnosed with hypertension, treatment with antihypertensives may be warranted. It is unclear how to best manage women with non-severe non-proteinuric pre-existing hypertension or gestational hypertension remote from term. Based on current evidence, arguments can be made both for and against allowing for tighter and ‘less tight’ (i.e. allowing higher blood pressure levels). There is insufficient evidence on which to base clinical decisions because of reporting bias and

Magnesium sulfate

Magnesium sulfate is a low cost, effective treatment for preventing and treating eclamptic seizures. The landmark trial, Magpie, conducted in 33 international centers showed that for women with pre-eclampsia (defined in the trial by BP 140/90 and 1 + proteinuria), magnesium sulfate reduced the risk of eclampsia by half (NNT = 100, 95% confidence interval 50–100).³⁷ Maternal mortality was also lower in women receiving magnesium sulfate (relative risk 0.55, 95% CI 0.26–1.14). Following the trial,

Summary

Pre-eclampsia remains a significant cause of maternal and perinatal morbidity and mortality in LMIC, although its exact prevalence remains unknown. While the principles of care are the same as in high resource settings, there are a number of challenges that must be considered in an LMIC setting. The main challenges include delays in triage, transport and treatment as well as the shortage of trained health care professionals. In order to address the global burden of pre-eclampsia and its

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Cited by (102)

Pre-eclampsia training needs of midwives in a Ghanaian tertiary hospital: A cross-sectional study
2024, Nurse Education in Practice
This study aimed to assess the specific clinical and non-clinical training needs of midwives and determine their preferred approach to enhancing performance.
Pre-eclampsia remains one of the leading causes of maternal deaths in low and middle-income countries. Pre-eclampsia-related deaths may be due to reduced midwifery knowledge and inadequate management. Therefore, a training needs assessment is vital in identifying gaps in practice, especially, in poorly resourced settings for maximal use of training resources.
A hospital-based cross-sectional study.
The largest tertiary hospital in Ghana.
An online version of the validated WHO Hennessy-Hicks Training Needs Analysis questionnaire was used to assess midwives’ training needs on the management of pre-eclampsia. The tool has good psychometric properties and was used to assess 1) midwives’ confidence in performing tasks, 2) the importance of the task to their role and 3) their preferred performance improvement approach. Data analysis adhered to the guidelines specified in the Hennessy-Hicks Training Needs Analysis Questionnaire and the priority training requirements of the midwives were assessed through descriptive statistics and a series of independent t-tests.
Among the 250 midwives who responded, most possessed 1–5 years of experience (74.7 %). All 28 tasks were viewed by midwives as essential responsibilities in pre-eclampsia management. Midwives had the greatest need for training in research/audit and clinical skills domains respectively (p < 0.001, 95 % confidence interval: 1.08–1.47, Cohen’s-D = 1.27; and p < 0.001, 95 % confidence interval: 0.69–1.06, Cohen’s-D = 0.87). The foremost primary training necessity, as recognised by midwives, was undertaking health promotion activities, including antenatal health education (MD= 0.43, 95 % confidence interval: 0.29–0.57). Training courses were identified as the preferred approach to address training needs and improve overall proficiency.
Midwives in Ghana require comprehensive training covering research and clinical-based competencies to improve pre-eclampsia management. Considering the pivotal role of Ghanaian midwives in safeguarding maternal well-being, there is a compelling need to enhance the calibre of midwifery services. These findings can guide stakeholders in countries with comparable healthcare contexts in creating effective, resource-efficient training programs that avoid counterproductivity, ultimately supporting national initiatives to enhance pre-eclampsia management and the quality of care.
Preeclampsia to COVID-19: A journey towards improved placental and vascular function using sulforaphane
2023, Placenta
Excess inflammation and oxidative stress are common themes in many pathologies of pregnancy including preeclampsia and more recently severe COVID-19. The risk of preeclampsia increases following maternal infection with COVID-19, potentially relating to significant overlap in pathophysiology with endothelial, vascular and immunological dysfunction common to both. Identifying a therapy which addresses these injurious processes and stabilises the endothelial and vascular maternal system would help address the significant global burden of maternal and neonatal morbidity and mortality they cause. Sulforaphane is a naturally occurring phytonutrient found most densely within cruciferous vegetables. It has anti-inflammatory, antioxidant and immune modulating properties via upregulation of phase-II detoxification enzymes. This review will cover the common pathways shared by COVID-19 and preeclampsia and offer a potential therapeutic target via nuclear factor erythroid 2-related factor upregulation in the form of sulforaphane.
Long-term neurodevelopmental follow-up of children exposed to pravastatin in utero
2023, American Journal of Obstetrics and Gynecology
Preeclampsia, especially before term, increases the risk of child neurodevelopmental adverse outcomes. Biological plausibility, preclinical studies, and pilot clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Obstetric-Fetal Pharmacology Research Centers Network support the safety and use of pravastatin to prevent preeclampsia.
This study aimed to determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child’s health, growth, and neurodevelopment.
This was an ancillary follow-up cohort study of children born to mothers who participated in the Obstetric-Fetal Pharmacology Research Centers Network pilot trials of pravastatin vs placebo in individuals at high risk of preeclampsia (ClinicalTrials.gov; identifier NCT01717586). After obtaining written informed consent (and assent as appropriate), the parent was instructed to complete the Child Behavior Checklist. To assess the child’s motor, cognitive, and developmental outcomes, a certified and blinded study psychologist completed child motor, cognitive, emotional, and behavioral assessments using validated tools. Given the small number of individuals in the studies, the 10- and 20-mg pravastatin groups were combined into 1 group, and the results of the pravastatin group were compared with that of the placebo group.
Of 40 children born to mothers in the original trial, 30 (15 exposed in utero to pravastatin and 15 to placebo) were enrolled in this follow-up study. The time of follow-up, which was 4.7 years (interquartile range, 2.5–6.9), was not different between children in the pravastatin group and children in the placebo group. There was no difference in the child’s body mass index percentiles per sex and corrected age, the rates of extremes of body mass index percentiles, or the report of any other medical or developmental complications between the 2 groups. No child born in the pravastatin group had any limitation in motor assessment compared with 2 children (13.3%) who walked with difficulty and 4 children (26.7%) who had reduced manual abilities in the placebo group. Moreover, children born to mothers who received pravastatin had a higher general mean conceptual ability score (98.2±16.7 vs 89.7±11.0; P=.13) and a lower frequency (15.4% vs 35.7%; P=.38) of having a score of <85 (ie, 1 standard deviation lower than the mean) compared with those in the placebo group. Finally, there was no difference in the parents’ report on the Child Behavior Checklist between the 2 groups.
This study reported on the long-term neuromotor, cognitive, and behavioral outcomes among children exposed to pravastatin in utero during the second and third trimesters of pregnancy. Although the data were limited by the original trial’s sample size, no identifiable long-term neurodevelopmental safety signal was evident with the use of pravastatin during pregnancy. This favorable neonatal risk-benefit analysis justifies continued research using pravastatin in clinical trials.
A prospective study of arsenic and manganese exposures and maternal blood pressure during gestation
2022, Environmental Research
Citation Excerpt :
For example, epidemiological studies report that exposures to particulate matter air pollution increases for BP in the third trimester by 2.11 mmHg (95% CI 1.34–2.89) (van den Hooven et al., 2011). Increases in blood pressure are precursors to serious pregnancy-related complications like pre-eclampsia which is one of the leading causes of death for pregnant mothers, especially in low-income countries around the world (Firoz et al., 2011). Maternal hypertensive disorders are common complications during pregnancy and one of the main causes of maternal mortality (Sibai et al., 2005).
Pregnancy is a sensitive time for maternal cardiovascular functioning and exposures to arsenic or manganese may adversely affect blood pressure (BP).
This study examined the associations between arsenic and manganese exposures and maternal BP measured during pregnancy. Effect modification by pre-pregnancy body mass index (BMI) was evaluated.
Pregnant women (N = 1522) were recruited for a prospective cohort study in Bangladesh (2008–2011). Exposure to arsenic and manganese was measured in drinking water at <16 weeks gestation and toenails at one-month postpartum. Systolic and diastolic BP were measured monthly. Linear mixed models estimated mean BP and differences in mean BP over gestation for arsenic or manganese exposures and adjusted for covariates.
Arsenic levels had an increasing dose-response association with maternal BP after 25 weeks gestation. Effect modification was observed for BMI. Participants with lower BMI (<23 kg/m²) exposed to 50 μg/L arsenic had 2.83 mmHg (95% CI:1.74–3.92) greater mean systolic and 1.96 mmHg (95% CI: 1.02–2.91 mmHg) diastolic BP compared to those exposed to ≤ 1 μg/L arsenic at 40 weeks gestation. Participants with higher BMI (≥23 kg/m²) showed a greater mean systolic BP of 5.72 mmHg (95% CI: 3.18–8.27 mmHg) and diastolic BP change of 6.09 mmHg (95% CI: 4.02–8.16 mmHg) at 40 weeks gestation when exposed to 50 μg/L compared to ≤ 1 μg/L arsenic. Participants with lower BMI exposed to drinking water manganese in the 2nd quartile (181–573 μg/L) had 1.04 mmHg higher mean diastolic BP (95% CI: 0.01–2.07 mmHg) at 40 weeks gestation compared to those in the 1st quartile (0.5–180 μg/L).
Arsenic exposures during pregnancy were consistently associated with increased average maternal systolic and diastolic BP. The effect of manganese on BP was less consistent.
A qualitative document analysis of policies influencing preeclampsia management by midwives in Ghana
2022, Women and Birth
Citation Excerpt :
To reduce maternal deaths and long-term disability, multi-disciplinary care is recommended for all women who develop complications, and the provision of prompt evidence-based treatment is essential [2,5–8]. In LMICs prevailing health disparities, technological challenges and lack of country-specific standard care policies make the application of interventions for PE management challenging [2,7,9]. Worldwide, overwhelming evidence shows that within their defined scope of practice, and regardless of the birth setting, midwives are pivotal in recognising deviations from normal and providing lifesaving interventions for both normal and high-risk pregnancies including PE and eclampsia [10].
Preeclampsia is a global issue that causes significant morbidity and mortality in low- and middle-income countries (LMICs). The care women with preeclampsia receive in LMICs is below the standard experienced by women in westernised countries due to multiple interacting factors. A review of policy factors influencing the management of preeclampsia in Ghana is needed.
This study focuses on the midwife’s role and scope of practice concerning preeclampsia management. The study aimed to explore the congruence between Ghanaian preeclampsia guidelines and international best practice recommendations for midwifery practice. The study also aimed to describe how recommendations are incorporated into Ghanaian guidelines.
This study was a qualitative document analysis of national and tertiary hospital policies related to midwives’ scope of practice in Ghana. Altheide’s five-step process (sampling, data collection, data coding and organisation, data analysis and report) was used to systematically source and analyse the content of written documents.
The findings illustrated several recommendation shortcomings in Ghanaian documents at the national and tertiary hospital levels. The content of Ghanaian preeclampsia management guidelines was not comprehensive, contained conflicting information, and was not backed by research evidence. The standards of practice for midwives were consistent at both the national and tertiary hospital levels. Midwives had limited roles in detection, management, stabilisation, and referral of women with preeclampsia.
Uniform guidelines incorporating international recommendations are urgently needed to improve multi-professional collaboration, solidify midwives’ roles, and optimise maternal and fetal outcomes.
A randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia
2021, American Journal of Obstetrics and Gynecology
Citation Excerpt :
Preeclampsia is a pregnancy-specific, multisystem disorder that affects 3% to 8% of pregnancies and remains a leading cause of maternal and neonatal morbidity and mortality worldwide.1,2
Preeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial support the safety and utility of pravastatin for the prevention of preeclampsia.
We previously reported the results of a phase I clinical trial using a low dose (10 mg) of pravastatin in high-risk pregnant women. Here, we report a follow-up, randomized trial of 20 mg pravastatin versus placebo among pregnant women with previous preeclampsia who required delivery before 34+6 weeks’ gestation with the objective of evaluating the safety and pharmacokinetic parameters of pravastatin.
This was a pilot, multicenter, blinded, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12+0 and 16+6 weeks of gestation were assigned to receive a daily pravastatin dose of 20 mg or placebo orally until delivery. In addition, steady-state pravastatin pharmacokinetic studies were conducted in the second and third trimesters of pregnancy and at 4 to 6 months postpartum. Primary outcomes included maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included maternal and umbilical cord blood chemistries and maternal and neonatal outcomes, including rates of preeclampsia and preterm delivery, gestational age at delivery, and birthweight.
Of note, 10 women assigned to receive pravastatin and 10 assigned to receive the placebo completed the trial. No significant differences were observed between the 2 groups in the rates of adverse or serious adverse events, congenital anomalies, or maternal and umbilical cord blood chemistries. Headache followed by heartburn and musculoskeletal pain were the most common side effects. We report the pravastatin pharmacokinetic parameters including pravastatin area under the curve (total drug exposure over a dosing interval), apparent oral clearance, half-life, and others during pregnancy and compare it with those values measured during the postpartum period. In the majority of the umbilical cord and maternal samples at the time of delivery, pravastatin concentrations were below the limit of quantification of the assay. The pregnancy and neonatal outcomes were more favorable in the pravastatin group. All newborns passed their brainstem auditory evoked response potential or similar hearing screening tests. The average maximum concentration and area under the curve values were more than 2-fold higher following a daily 20 mg dose compared with a 10 mg daily pravastatin dose, but the apparent oral clearance, half-life, and time to reach maximum concentration were similar, which is consistent with the previously reported linear, dose-independent pharmacokinetics of pravastatin in nonpregnant subjects.
This study confirmed the overall safety and favorable pregnancy outcomes for pravastatin in women at high risk for preeclampsia. This favorable risk-benefit analysis justifies a larger clinical trial to evaluate the efficacy of pravastatin for the prevention of preeclampsia. Until then, pravastatin use during pregnancy remains investigational.

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11Pre-eclampsia in low and middle income countries

Section snippets

Definition of LMIC

Epidemiology of pre-eclampsia in LMIC

Overview of challenges in LMIC

The role of task shifting

Prevention of pre-eclampsia

Detection of pre-eclampsia

Antihypertensives

Magnesium sulfate

Summary

Lancet

Lancet

Lancet

Lancet

Workshop on magnesium sulfate for the management of pre-eclampsia and eclampsia

Millennium development goals

WHO systematic review of maternal mortality and morbidity: methodological issues and challenges

BMC Medical Research Methodology

WHO Family of International Classifications Network Meeting

Beyond the numbers: reviewing maternal deaths and complications to make pregnancy safer

Antenatal care in developing countries. Antenatal care in developing countries: promises, achievements and missed opportunities: an analysis of trends, levels and differentials, 1990–2001

Women on the front lines of healthcare

Linking families and facilities for care at birth: what works to avert intrapartum-related deaths?

International Journal of Gynecology and Obstetrics

Health workforce skill mix and task shifting in low income countries: a review of recent evidence

Human Resources for Health

11
Pre-eclampsia in low and middle income countries