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Maternal and Child Health Integrated Program (MCHIP)

Report of Second Technical Working Group Meeting on Pre‐eclampsia/Eclampsia

Washington, D.C., November 18 – 19, 2009

Introduction Since its inception in 2008, The Maternal and Child Health Integrated Program (MCHIP) has played a leading role in assisting USAID and other global partners to find effective approaches to prevent and treat pre-eclampsia/eclampsia (PE/E) at global and country levels. MCHIP convened the First Technical Working Group Meeting on Pre-eclampsia/Eclampsia in April 2009. Over 40 clinicians, policy makers and program implementers attended this meeting. MCHIP continues to play a role in implementing interventions designed to achieve results as specified in USAID’s pre-eclampsia/eclampsia results pathway. In order to continue the discussion that began at the first meeting, a Second Technical Working Group Meeting was held November 18-19, 2009. The goal of this meeting was to expand the group formed at the first conference through inviting a larger number of international participants and presenters, particularly those from developing nations. The second meeting also provided a discussion forum for the small working groups which were formed at the first meeting. Summary Report Almost 80 researchers, clinicians, advocates/policy-makers, programmers and implementers from 38 organizations in 12 countries participated in the Second Technical Working Group Meeting.1 The objectives of the meeting were to:

• Provide updates on state of the art technical and program knowledge in prevention and treatment of pre-eclampsia/eclampsia in low resource settings.

• Provide a forum for the PE/E Small Working Groups to meet and finalize their scopes of work for the coming year.

• Determine how the PE/E Technical Working Group can act as a catalyst to advance knowledge and programming with the goal of contributing to the reduction of mortality from PE/E in targeted countries.

Highlights of the meeting included technical presentations on prevention of PE/E through calcium supplementation in pregnancy, treatment of PE/E with magnesium sulfate and anti-hypertensives and presentations of country level prevention and treatment programs in Burkina Faso, Chile, Sri Lanka and Nepal.

1 See Participant List, Annex 3

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Session Summaries _______________________________________________________________________ Day 1 Introduction and Opening Remarks Leslie Mancuso, Jhpiego President and CEO, thanked all the donors whose contributions made this

meeting possible and then thanked all participants for attending. Nahed Matta, from USAID’s Maternal and Child Health (MCH) Bureau and lead Agreement

Officer’s Technical Representative (AOTR) for MCHIP, stated that the USAID MCH team supports pre-eclampsia/eclampsia programming, and that individuals need to pay attention to the neglected area of pre-eclampsia/eclampsia. Several other USAID projects and the USAID MCH Global Health Initiative working group will also be focusing on this area.

France Donnay, Program Officer with the Bill and Melinda Gates Foundation, stated she was excited to work with MCHIP to advocate for increased attention and commitment to pre-eclampsia/eclampsia, and discussed the Foundation’s current MNCH strategy.

Erin Sines, Program Officer with the John D. and Catherine T. MacArthur Foundation, welcomed the group and discussed the past pilot grant-making work that the Foundation performed related to pre-eclampsia/eclampsia, with a specific focus on the Foundation’s work in Kano State, Nigeria.

• Patricia Gomez presented the meeting objectives and reviewed the meeting agenda. Participants also introduced themselves; a detailed Participant List can be found in Annex III. Dr. Harshad Sanghvi then presented an overview of pre-eclampsia/eclampsia entitled “We can

prevent mortality and morbidity from pre-eclampsia”. According to Dr. Sanghvi:

• Currently, there is no inexpensive and effective way to predict who is likely to get pre-eclampsia; all women are potentially at risk. Prevention and early detection of pre-eclampsia/eclampsia is vital for all women.

• Calcium and aspirin are, to date, the only promising interventions for prevention of pre-eclampsia/eclampsia.

• The main question to address is how to make calcium more acceptable and affordable. • Challenges in detecting pre-eclampsia through BP measurement and proteinuria

measurement are due to lack of resources and logistical mechanisms; need to make affordable interventions available.

• Solid guidelines are needed for management of pre-eclampsia. • Magnesium sulfate has a huge role to play in the prevention/treatment of eclampsia but we

have not been able to universalize the use of magnesium sulfate. • To decrease mortality we must take the treatment for eclampsia to where the woman gives

birth. Technical and Programmatic Presentations Session I: Primary Prevention of PE/E Dr. Fernando Althabe, Instituto de Efectividad Clinica y Sanitaria, Buenos Aires: What is the ideal primary prevention intervention?

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• The ideal prevention strategy is one that eradicates pre-eclampsia and is safe, affordable, easy to administer, and culturally acceptable. We have not yet achieved this ideal.

• Low dose aspirin and calcium supplementation are the two interventions that have been proven to be effective in reducing the risk of pre-eclampsia and reducing maternal death.

• Provision of calcium supplementation has also shown proven benefits for infants and children through reducing their blood pressure.

• Reduction of blood pressure from calcium helps to reduce complications of severe pre-eclampsia.

• Finding creative ways to supply calcium to populations, such as food fortification, is a priority and probably holds the greatest promise.

• Calcium intake among women in developing countries is less than the recommended intake and less than the intake of women in developed nations.

• Future research should be conducted to assess the effect of calcium supplementation in pre-pregnancy states.

Dr. Vicente Bataglia, Universidad Nacional de Asunción, Paraguay: Experience with Calcium Supplementation in Latin America

• Pregnancy requires high calcium levels, with the highest being in the third trimester; calcium absorption is increased during pregnancy.

• Eclampsia, pre-eclampsia and pregnancy-induced hypertension may be associated with calcium metabolism.

• In Latin America, strategies to reduce hypertension have received considerable attention and an inverse relationship between calcium intake and hypertension in pregnancy has been seen since the 1980s.

• In Latin America, studies of calcium intake during pregnancy showed that, independent of the method used, there was a lower intake of calcium during pregnancy than recommended by the national Food and Nutrition Board.

• Research has suggested that fortification of food might make the benefits of calcium available to all women, not just those receiving antenatal care.

Discussion Questions and Answers Have any calcium supplementation or fortification programs moved forward or has this remained a research protocol?

• Dr. Bataglia mentioned there were no such programs in Paraguay. What is the possible detrimental effect of both calcium and low dose aspirin?

• There have been no large, randomized factorial designs/studies to glean evidence from. There is no magic bullet for pre-eclampsia.

Can you tell us a little more about the seven studies on implementation of calcium supplementation? • There are two large trials out of those seven – the Belizán trial in 1991 and the WHO trial in

2006 in Asia, Africa and Latin America. The largest trial to date, the WHO trial, can probably be generalized to all those settings. The WHO trial didn’t show a relative effect on hypertension and pre-eclampsia, but showed an important effect on maternal complications due to these conditions.

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Can you quantify low calcium intake and at what point does calcium intake stop being beneficial? • It is unknown what happens with long-term supplementation and intake of lower doses. The

question of the minimum dose and time period still needs to be answered. There is much reticence in the medical community to give low-dose aspirin.

• No additional clinical efficacy trials need to be undertaken. The relative risk reduction is the same regardless of risk (low risk v. high risk pregnancy).

How widespread is calcium deficiency?

• The WHO study found uniformly in Latin America, Africa and Asia significant levels of calcium deficiency. There is no doubt that there is generalized calcium deficiency.

Can calcium and aspirin really reduce all maternal mortality by 20%? Is that right?

• This figure was related only to hypertensive disorders. Session II: Secondary Prevention— Detection of Pre‐eclampsia

Dr. Alfredo Fort, MACRO International, Calverton, MD: Are facilities and providers ready to detect pre-eclampsia during antenatal care: what do SPA data tell us?

• The Service Provision Assessment (SPA) is a nationally representative survey of the formal system of health care that collects information on the readiness of a facility based on inventory, observations, client exit interviews, and health worker interviews. It differs from the DHS or other population-based survey statistics in that it describes the process indicator rather than the impact or final outcome.

• According to SPA results, there is very low “readiness” to detect and manage PE/E in East Africa/Ghana:

o Capacity Most facilities have equipment to measure blood pressure but the capacity of

these facilities to detect proteinuria is inconsistent and insufficient. There is low availability of anticonvulsants (at least in the delivery room).

o Providers Providers receive little support in the form of guidelines or training, which is

reflected in poor counseling to clients. o Clients

Clients are unaware of the risk symptoms for seeking help. o Performance

Anticonvulsant use is the least performed signal function of basic emergency obstetric and newborn care (BEmONC).

• Worldwide levels of ANC are very high with women having at least one ANC visit during their pregnancy. This presents an opportunity to detect PE/E and to educate women on the disease. Improving capacity to detect and manage PE/E should contribute to reducing obstetric case fatality rates and, potentially, overall maternal mortality.

Dr. Harshalal R. Seneviratne, University of Colombo, Sri Lanka : Detection and treatment of pre-eclampsia/eclampsia in Sri Lanka

• Detection, management and treatment of pre-eclampsia/eclampsia in Sri Lanka were achieved to a high level of efficiency because of the organized health care structure developed and

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sustained from the early 20th century. Services were divided between curative and preventive branches with very effective interaction between the two.

• Lessons learned from Sri Lanka’s experience: o Blood pressure checks should evolve as a routine practice in clinical care. o Establish quality antenatal clinics at the primary level of care in the community,

preferably including a home visit service as well. o Ensure use of sphygmomanometers by supply of the appropriate equipment for the

locality and adequate training of staff. o Parallel establishment of the specialist service is necessary. o Development of non-health facilities, such as transport and communications, will

enhance the reduction of all maternal deaths, including those due to hypertension.

Discussion Questions and Answers Was any emphasis given to calcium supplementation for prevention of PE/E in Sri Lanka?

• Dr. Seneviratne said that calcium is not given pre-pregnancy in Sri Lanka. It is provided to women, along with iron, beginning in the 20th week and continuing through the remainder of the pregnancy.

The SPA results Dr. Fort presented showed that for the past three years providers have not received training. However, health workers may not answer the question truthfully because they expect to be offered training if they deny having received it.

• Dr. Fort explained that before starting interviews there is an informed consent process and participants are told that their names will not be collected or connected to their responses. While other factors may affect their answers, the aggregate data shows that, on average, percentages of training for health workers attending deliveries is very low.

What is the relationship between institutional deliveries versus home deliveries in terms of Sri Lanka’s experience with PE/E?

• Dr. Seneviratne said that colleagues in the region have criticized Sri Lanka for over-medicalizing their health system. Recent statistics on deliveries show that 4.1% took place in private hospitals, 1.5% in the ‘home’ (mostly in Internally Displaced Person camps), and all others at government institutions. In 2007 it was decided that midwives who were working in the field would also be required to work in the hospital every three years for a term of at least six weeks. Health promotion and education takes place in local clinics while deliveries tend to be referred to main hospitals.

Session III: Treatment of Pre‐eclampsia Dr. Peter von Dadelszen, University of British Columbia, Vancouver, Canada: What is the ideal hypertensive agent for PE/E?

• The ideal hypertensive agent is orally administered, forces a reliable and smooth reduction in blood pressure (within one hour) without overshoot, has a rapid onset and a preferential vascular CNS effect and does not result in maternal or fetal toxicity.

• Magnesium sulfate is not a hypertensive. • Calcium channel blockers (CCBs) are more reliable than hydralazine in lowering blood pressure

in women with severe hypertension. Hydralazine is more reliable than labetalol in reducing severe hypertension.

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• Antihypertensive use in women with non-severe pregnancy-induced hypertension reduces the risk of developing severe hypertension. The effect is consistent across all classes of drugs.

• Minimal overshoot: BP should be in range of 130-160 mm Hg systolic and 80-110 mm Hg diastolic; CCBs and beta-blockers are less likely to cause overshoot than hydralazine.

• An intervention should include one or two oral antihypertensive agents; the choice for a single hypertensive lies between nifedipine and labetalol.

Professor Lelia Duley, University of Leeds, United Kingdom: Treating Severe PE

• There is no consensus about the definition of severe pre-eclampsia. However, the Magnesium Sulfate for Prevention of Eclampsia (Magpie) trial determined several criteria based on medical history and examination.

• Providers need to have awareness and training surrounding severe pre-eclampsia in order to make the diagnosis, and then perform subsequent history and medical examination.

• Systematic review of 6 studies (including the Magpie study) shows that magnesium sulfate probably reduces the risk of maternal death and substantially reduces the risk of severe and non-severe pre-eclampsia. There is no significant effect on the outcome for the baby (except assurance that it is safe).

• Side effects have been shown to result from magnesium sulfate; the most common is flushing and problems at intramuscular injection site.

• In the “lowest” economic tier of developing countries analysis of the Magpie study found it was most cost effective to limit treatment with magnesium sulfate to cases of severe pre-eclampsia. The cost-effectiveness increases if magnesium sulfate is made freely available.

• There is a reduction in the risk of maternal death and recurrent convulsions when using magnesium sulfate compared to diazepam or phenytoin. Magnesium sulfate is the drug of choice for eclampsia.

• Magnesium sulfate is an example of market failure - there is no commercial incentive to manufacture and distribute magnesium sulfate.

• There is insufficient evidence regarding the timing of delivery for early onset pre-eclampsia. Dr. Matthews Mathai, World Health Organization, Geneva: Timing of delivery and induction of labor in pre-eclampsia

• In general, most people would plan an early delivery with severe disease. If onset of pre-eclampsia is closer to term, delivery is more likely to be at term.

• Cochrane studies on expectant care for severe pre-eclampsia before term show that there are insufficient data for reliable recommendations on induction in women with severe early onset pre-eclampsia. Further large trials are needed.

• The only large trial related to mild pre-eclampsia and induction showed that induction of labor is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks gestation.

• The recommendations from the WHO manual Managing Complications in Pregnancy and Childbirth, published in 2000, have not changed much. The guidelines state that delivery should occur within in 24 hours of onset of eclampsia, and induction should take place after week 37 for cases of mild pre-eclampsia.

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Discussion Questions and Answers Although labetalol is used as a first drug of choice in many institutions, it is less familiar to health providers. How many women have been randomized to control trials with labetalol?

• There is considerable experience with labetalol and RCTs have taken place. There is no concern about safety especially surrounding the management of severe hypertension. There have been no studies with data from the developing world.

How many times in Dr. Duley’s research has she had to use calcium gluconate to reverse ‘harmful’ effects of magnesium sulfate?

• A very small number of times. In the eclampsia trials, the use of calcium gluconate was the same in all the intention arms. In the Magpie study the use was very low. This needs careful evaluation if magnesium sulfate is rolled out.

When we don’t have good evidence, what kind of guidance can we give to our most peripheral providers about when to terminate pregnancy, when to start a particular drug? What can we do in the presence of our uncertainty of information?

• The trials have all been conducted at tertiary and secondary levels – the evidence at these settings is clear. It’s much harder to know how far you can safely generalize to primary care and community care settings. One issue with giving magnesium sulfate at primary and community care settings is it may serve as a barrier to transport: if a woman is given magnesium sulfate where she is, health workers may be under the impression that it is safe for her to stay where she is even though she may need to be transported.

• We need a better definition of what severe disease is and we need to define it against a raft of outcomes.

• If we do this right, we will learn from practice uncertainty or practice variability. If we develop data collection and surveillance of not just demographics and outcomes but interventions women received, then we’ll know which interventions affect outcomes.

In facilities in developing countries where magnesium sulfate is being used, do we know what proportion is being used for treatment as opposed to prophylaxis?

• Good data do not exist. The priority for low-income countries is to use it for treatment first. In the UK, it is used sparingly for prevention in women with severe pre-eclampsia only.

The hydralazine/labetalol trials are all IV trials and the potency and the pharmacodynamics differ between oral and IV routes of administration. It may not take much effort to bring new drugs into a country – if you look at the formulary the classes may be there. What Peter said about CNS sparing drugs is very important – we are learning more about the pathophysiology of brain injury and that pure vasodilators may be bad. There are different "epochs” of care in treating hypertension– before the acute episode/pre-partum, intrapartum and postpartum. What is included in “black” women when it was stated that black women are resistant to beta-blockers?

• The racial group or being genetically derived from the African continent, sub-Saharan African versus Northern African. There is a genetic resistance.

Is the recommendation of the WHO/MCPC, to only classify pre-eclampsia on the basis of diastolic blood pressure, valid?

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• According to the WHO, yes, it’s an important factor. The diastolic blood pressure is important in helping us make our decisions.

• The Canadian guidelines used to say the same thing and were re-written. In developed countries as women age, systolic blood pressure is increasingly going to become a clinical issue, and several studies show that there is a point of inflection of risk with a systolic above 160. Dr. von Dadelszen thinks that systolic blood pressure is an important issue as maternal weight and obesity becomes an issue internationally.

In the UK things did a complete change within a year. Was there any one thing in the UK that made clinicians adopt this change and start adopting new practices?

• There was a large meeting held which was attended by over 3oo obstetricians from around the country that discussed the research results regarding magnesium sulfate. If we had used serum levels for monitoring, it would have been a barrier to implementation in the UK. There was also a high awareness of evidence-based practice.

Session IV: Eclampsia Dr. Joseph Ruminjo, EngenderHealth, New York: Addressing eclampsia: Expanding use of magnesium sulfate: Meeting the Challenge

• Based on scientific evidence, WHO recommends injectable magnesium sulfate for treatment of pre-eclampsia and eclampsia. It has been the standard in the developed world for more than 20 years and is the safest, most effective and lowest-cost medication for treating the disease. However, magnesium sulfate has not become standard treatment in many countries.

• At a meeting organized by EngenderHealth and the University of Oxford in 2007, experts identified the following key barriers to availability and use of magnesium sulfate for treatment of pre-eclampsia and eclampsia:

o Lack of political will, national policy, prioritization and guidelines and/or lack of their implementation

o Shortage of trained health care professionals o Scarce supplies of magnesium sulfate and poor logistic systems

EngenderHealth, the University of Oxford and the John D. and Catherine T. MacArthur Foundation made a joint commitment as part of the Clinton Global Initiative to address these barriers.

• The University of Oxford designed an e-learning module to train health professionals in the management of eclampsia and pre- eclampsia, including how to administer magnesium sulfate. A pilot study is currently being conducted in Nigeria, Mexico and India. There are future plans to extend coverage of the module worldwide and to develop similar modules on other aspects of maternal and neonatal care.

Professor Helen de Pinho, AMDD, Columbia University, New York: Task shifting in eclampsia management Notes will not be shared by request of the presenter. Dr. Rashida Begum, Dhaka Medical College and Hospital, Bangladesh: Single dose treatment and community approaches with magnesium sulfate

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• Early administration of magnesium sulfate in severe pre-eclampsia can prevent development of eclampsia and complications.

• In Bangladesh, magnesium sulfate has been used as a first line anticonvulsant since the beginning of 1998. There is a low dose protocol for Bangladeshi women: 4 gm IV and 6 gm IM as loading dose then 2.5 gm IM 4 hourly in alternate buttock for 24 hours. Even with this low dose, serum magnesium level remained within effective therapeutic range (between 2.1 mg and 6 mg/dl). Moreover, the level was well below toxic level.

• There is no statistically significant difference between the loading dose and standard regime. The loading dose reduces total dosage, and pain and complications following intramuscular injections. Any health worker can use a single dose of magnesium sulfate to prevent or control convulsion before referring to a higher center. Treatment of eclampsia is, thus, possible even in the home.

Discussion Questions and Answers What was the genesis of providers’ fears regarding toxicity (going beyond the loading dose of magnesium sulfate)?

• Dr. Harshad Sanghvi said there is an unreasonable fear among providers that magnesium sulfate has a very narrow margin of error and is a dangerous drug. This perception is compounded by systems that require providers to carry out rather extensive monitoring when repeat doses are administered. Lelia’s data showed that only a few patients out of the thousands in the study actually required reversal using calcium gluconate. From a public health perspective, you could do away with reversal because it is not necessary for a vast majority of patients. The champions who start using magnesium sulfate and show it is safe are going to convince other providers that it’s safe.

Why did some of the patients who were given magnesium sulfate die?

• Dr. Begum said there were no liver, renal, heart failure, or obstetric complications. Clinically there was no identifiable cause.

Did anyone try to replicate the finding that a single loading dose is as efficient as the traditional treatment? Are there examples in other countries where similar protocols have been investigated?

• Dr. Peter von Dadelszen shared that an abstract was presented at FIGO that found similar results in northern Nigeria when following the “Dhaka protocol” (administering a single loading dose).

• Professor Lelia Duley pointed out that ‘toxicity’ is not a suitable term because it generates anxiety. The adverse effects of the drug are often very similar to complications of the condition. She said she would be hesitant to give magnesium sulfate without clinical monitoring and reiterated the importance of a very large study to determine if the lower dose is as effective as the standard treatment.

What does the study mean for the policy makers in the audience? Have you been discussing scaling up the loading dose through community health workers or are you looking for more studies before you are able to make policy decisions?

• Shah Monir Hossain said the ICDDR,B (International Centre for Diarrheal Disease Research, Bangladesh) is duplicating the Dhaka study in a hospital setting. These results will help develop national guidelines for Bangladesh.

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Session V: Country Perspectives Claudia Vera, Chilean Health System, Viña del Mar, Chile: Community and cultural aspects of eclampsia

• In Chile, researchers have observed that late interventions in pre-eclampsia have been shown to increase rates of eclampsia. In Chile, women do not attend the health clinic when the danger signs appear.

• Abortion and emergency contraception are illegal in Chile, so women must carry unwanted pregnancies to term.

• Domestic violence, familial abuse, poverty and high rates of teenage pregnancy prevent women from seeking early care.

• Low-income women don’t trust the Chilean Health System or don’t have time to go to the health clinic, and refuse hospitalization and emergency care.

• A Chilean organization, Crece Contigo (Child Grows With You) was designed in 2007 to accompany, protect and deliver integrated support to all pregnant women at risk through focalized actions to vulnerable families.

Dr. Shilu Aryal, Ministry of Health and Population, Nepal: Addressing maternal mortality from eclampsia: Community-based interventions in Nepal

• Nepal has experienced a dramatic decline in maternal and child mortality in the past 15 years.

• In 1998, eclampsia was the third leading cause of death in Nepal. The 2008 Morbidity and Mortality study shows that eclampsia will move up as a cause of death since postpartum hemorrhage is being tackled by use of preventive measures such as active management of third stage of labor.

• The majority of women deliver at home without a skilled provider and Nepal has had success with low-cost, low-scale interventions, such as iron supplementation.

• Nepal has a comprehensive approach designed to prevent mortality from pre-eclampsia. Primary prevention includes calcium distribution and education by female community health volunteers (FCHVs); secondary prevention includes detecting pre-eclampsia and timely delivery and ensures no missed opportunity to perform a urine protein test; and tertiary prevention includes treatment of severe pre-eclampsia with magnesium sulfate.

• Currently, two village development committees have been selected to carry out calcium acceptability tests of calcium tablets versus powder.

Prof. Blami Dao, Souro Sanou Teaching Hospital, Polytechnic University of Bobo Dioulasso, Burkina Faso: Improving Quality of EmONC and PE/E Management in Burkina Faso

• Magnesium sulfate was reintroduced to Niger, Guinea, Burkina Faso and Rwanda in 2004-2005. There was some resistance in Cote d’Ivoire.

• In Burkina Faso, magnesium sulfate was initially purchased from neighboring countries, and route of injection was changed from IM to IV to avoid having to mix the IM dose with lignocaine, a local anesthetic.

• In 2008, through advocacy of two leading teaching hospitals, the drug has become available nationwide in Burkina Faso and is included in eclampsia treatment kits in all public hospitals.

• Through more aggressive treatment (the use of magnesium sulfate in severe pre-eclampsia) there has been a decrease in maternal and neonatal morbidity from pre-eclampsia/eclampsia.

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• Stock-outs of magnesium sulfate still exist in some hospitals and some obstetricians resist using magnesium sulfate.

Discussion Questions and Answers Dr. Shilu, can you tell me more about the 90 days and 1 gram? Is that about acceptability? How did the study set about what would be the outcome during pregnancy for that dose that we are looking at?

• The 90 days is only for the study to compare the different formulations. The acceptability issue arose around assessing preference in using tablets versus the powder. Women will take a pill for a month and then switch to the sachet for a month and will be asked which they preferred. After 6 months, we will assess the ability of the system to reach every woman within the health system.

• Nepal is not testing efficacy of intervention. The intention is in the next several months to implement at the full district scale.

Professor Dao – after training in the region were you able to follow-up after training? Is a regional training approach sufficient to get things going? What more can we learn?

• Three months after the training we went to each of these six countries to see how they are implementing. In five out of six countries magnesium sulfate was used. In only one country people were reluctant. It is good to bring people together to make a commitment, and then at the follow up when we see how countries are doing things, countries are eager to move forward.

Is there now free-flow of magnesium sulfate in Burkina Faso? Is it on the national drug list so it can be used whenever it is needed in different cases?

• It is not on the national lists but is available through a national agency. Should we start to offer 1 gram of calcium carbonate for 90 days after 4 months of pregnancy in my home country?

• Harshad has analyzed 12 roadmaps that WHO has put in place and in every one, the potential exists for calcium distribution. In some it’s in the plan itself, and in others it’s an evidence- based practice that should be considered for countries to introduce.

• The North American experience has shown that a large randomized trial didn’t show any effect at all. Different communities may have different responses. The answer may not be as clear cut as we thought.

• There is always a change from efficacy to effectiveness when something seen in a clinical trial is put into programs on ground. Is anyone taking advantage of these programs as they roll out? We can’t just assume the programs work. People need to take advantage of these launches to put evaluation in place.

• How do you get implementation of policies? Helen de Pinho would encourage documentation on the uptake of magnesium sulfate. If we look at the rollout of calcium we should look at what the lessons are and how we translate them.

• We may need some more work to characterize the populations in which this is effective. • In Nepal we have a strong iron/folate program, and we think calcium supplementation could

achieve similarly high coverage. • There may be an opportunity here – WHO is embarking on a review of the evidence. As part of

this they get scoping questions. From the point of view of working groups there may be an

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opportunity to look at some of the questions that are emerging – dosing, when to start, and see if the questions can be formally reviewed.

• Any time you roll out a program, it happens in different institutions at different times. If you can collect data across all sites during implementation, then you will have the knowledge at the end of the implementation process to know whether you altered the incidence of the diagnosis of pre-eclampsia. You must also track all perinatal outcomes.

It is challenging to develop protocols in West Africa. Are these protocols only for the hospital or do they include lower level health facilities? Is it just for the teaching hospitals? • So far these guidelines are being used at the district/hospital level, not the primary health care

facilities. They still believe in a lot of Francophone countries that the effective dose is not far from the toxic dose so there is a lot of reluctance to use it at the peripheral level.

In preparation for small group work, participants were asked to split into their groups and refer to the instructions for the small group work that were placed in the meeting folder. Day 2 Patricia Gomez, MCHIP, Washington, DC: Recap of Day 1

• Calcium is an evidence-based and feasible intervention for the prevention of PE/E in low-resource settings.

• Detection of PE in maternity care settings needs improvement through provision of adequate equipment, supplies, and guidelines on their use.

• National commitment to improving the health care structure will lead to improved detection, treatment, and overall outcomes for women with PE/E.

• Treatment of women with PE/E must take into account issues of which antihypertensive agents to use, when to deliver, and when and how to use magnesium sulfate.

• Scaling up of magnesium sulfate remains a challenge and issues like task shifting and use of magnesium sulfate in very peripheral settings needs serious consideration.

• Psycho-social and cultural influences on care seeking must be taken into account as we determine how to scale up quality care.

Session VII: What the data tell us about where we are and where we need to go

Dr. Harshad Sanghvi, Jhpiego, Baltimore: What do maternal mortality audits show?

• Of 46 African countries, 36 have critical staff shortages. An increase of 139% is needed to meet 2005 level of need. This is not likely to happen unless we:

o Double training output o Make a serious commitment to task shifting/sharing o Revamp HR policies including retention and reward

• Jhpiego and the CDC carried out an assessment of general and minor surgery in Mozambique and found that surgeons there are performing at 20% of the expected productivity.

o Just increasing the workforce does not automatically lead to increased access to care. o Many facilities lack supplies required to make health providers productive.

• Standards Based Management and Recognition (SBM-R) is a QI approach Jhpiego utilizes that allows providers to use evidence-based standards in their own settings and monitor them, with rewards for achievements.

• Lessons from performance audits:

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o Performance is maintained for longer periods • if training was competency- based • If performance standards are clear and agreed on

o High performance more likely if there is more than one trained provider at the site (peer support)

o Performance deteriorates sharply with excessive workload Dr. Fernando Althabe, Instituto de Efectividad Clinica y Sanitaria, Buenos Aires, Argentina: Summary of meeting on evidence-based scaling-up to improve maternal and perinatal health, CIHR, WHO and NIH Workshop Ottawa, September 24-25, 2009.

• The purpose of the meeting was to identify scaling-up strategies and evaluation frameworks that are both scientifically sound and acceptable for policy makers and research funders. The initial focus was on magnesium sulfate for treating eclampsia and calcium supplementation for preventing PE/E.

• A 50% increase in the use of magnesium sulfate would prevent 10-15 maternal deaths per 100,000 live births.

• A strategy was developed to evaluate the effect of emergency kits on improving PE/E outcomes. Settings and population of study:

o Countries with magnesium sulfate licensed and available or committed to (3-4) o Medium/Large Hospitals (because they have high rates of eclampsia: 20 cases per

year) o Low use of magnesium sulfate: <20% use (WHO Global Survey 2010) Outcomes: o Primary

use of magnesium sulfate in women with eclampsia o Secondary:

Eclampsia-related death or severe morbidity Neonatal death or severe morbidity

• There is no clear agreement on the need to scale up calcium supplementation. There is more agreement on the need of research relating to: o Methods to supplement populations, including fortification o Pre-pregnancy and early pregnancy supplementation

Eleni Tsigas, Pre-eclampsia Foundation, Minneapolis: Advocating for the Patient: Where does she need us to go?

• The Pre-eclampsia Foundation goals include: o Faster diagnosis o Better care o Healthier outcomes

• The Pre-eclampsia Foundation’s website is the #1 online source of information on pre-eclampsia.

• Patients care about: o Patient information that impacts their understanding of when and how to seek

care o Support to deal with traumatic pregnancies and outcomes o Qualified and accessible healthcare providers and resources

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o Accurate information, access to care, and lifestyle reminders to positively impact our long term health and that of our babies

• Less than 50% of women (primarily in the U.S.) who have access to prenatal care understood the description of pre-eclampsia as it was explained to them

• The “Jamaica card” education tool provides focus for antenatal education on PE/E and appropriate response to these symptoms for both patients and providers.

Discussion Questions and Answers How can we work on the issue of performance— is it an issue of guidelines or is there more than that?

• Dr. Sanghvi said that any kind of performance system needs to be internally driven and the best way to do this is to set targets and reward success. The process Jhpiego is using starts with acceptance of certain standards in setting goals for the facility or an individual to follow, helps them measure themselves against those guidelines, determines the gap between desired and actual performance and what specific actions should follow. Another key is sharing results of standards with neighboring facilities as a degree of competition follows.

During Dr. Sanghvi’s presentation he made a statement that performance clearly deteriorates with workload. Has anyone looked into what is the minimum package that we should be asking community health workers to deliver before we say, “It’s enough?”

• Steve Hodgins said the community health worker cadre in Nepal is volunteer-based and over the years various functions have been added onto their responsibilities. In practice when you speak with the CHWs, they almost invariably say “Give me more responsibility.” Their status in the community reinforces their willingness to take on new roles.

• Eleni Tsigas said the Pre-eclampsia Foundation has had success turning survivors into providers. If women have been connected with others to help them through the post-traumatic process, they not only heal but also turn into providers themselves.

Session VIII: Report from Working Groups Each working group presented the key issues that they discussed. The working groups should share reasonable areas for continued work. There was a presentation from each group and a brief discussion. Policy and Advocacy, Anne Hyre, ACNM

• There is some global consensus (WHO statement) on pre-eclampsia/eclampsia. • FIGO and ICM will look at global statement and decide whether FIGO and ICM should develop

an additional statement and/or use statement and distribute to member organizations. • Would like to see simple briefs on management of eclampsia/pre-eclampsia and create

something that is user friendly for providers. • Advocate to MCHIP and others to come up with international consensus on antihypertensive

use. • Work with ME&R group to contribute to data collection tools; draw upon POPPHI tools and

use some of that to contribute to data collection tool to gather information about country level guidelines and policies (2009-2010).

• Bring together country level teams to one meeting to disseminate results of survey, review evidence and to advocate for change (2009-2011).

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• Advocate for additional support to in-country professional organizations. Community Approaches, Peg Marshall, USAID

• Get together with the group from the first meeting and have a merged membership. • Lack of awareness, lack of solutions at community level, skills of health workers working in

primary health care. • Supplies and drugs flowing to the periphery – how to get drugs and supplies to the far

periphery? • Focus on the four delays – lack of recognition of a problem, lack of decision making, bringing

healthcare into the periphery. • Interventions: Calcium, stabilization factor (magnesium sulfate alone vs. transferring or do we

need antihypertensives closer to community). • Cost funding schemes and community funding for emergencies. • Avoidance of too rapid discharge of women going whom who are unaware of danger signs. • Protein and blood-pressure self testing in the community (need more options that can be

utilized in the periphery. • Cheaper, simpler lab tests that can be brought closer to the community. • Will hold a telecom with first group to merge issues and develop a more concrete workplan.

Standards, Training and Quality Assurance, Dr. Abdelhadi Eltahir, Pathfinder

• Completed gap analysis and decided upon five gaps: lack of provider knowledge, lack of standardized clinical guidelines, lack of implementation of national policies, lack of implementation of enabling policies and gap in performance measurement.

• Need to identify and review current evidence on PE/E. • Review and develop draft clinical guidelines on PE/E, including guidelines. • Review existing training modules. • Develop draft training curricula for identified cadres. • Develop draft standards of services, quality indicators and measurement processes. • Need to consider further the terms of reference; this will be a work in progress. • How to coordinate and communicate between the co-chairs of each of the working groups

since there are overlapping issues. Drugs and Devices, Thomas Easterling, University of Washington

• Diagnostics – reduce delays in seeking care o Established (measuring BP, urine dipstick) versus novel ideas o Simplified BP measuring (only systolic alone)

• Novel: alternate measurement for proteinuria, measuring urine instead of BP primarily • Low resource diagnostics: Many tests require sophisticated lab equipment and low resource

diagnostics are on the horizon • Can we build a culturally adjustable card? • Gaps: Will women move towards care? What is the algorithm of care? • Devices

o IV access more acceptable to women than IM route o Induction of labor is the main cure for the disease – need means to get the baby out.

Devices such as Foley bulbs can assist with induction of labor. o Pumps that can safely deliver IV magnesium sulfate

• Drugs o Data short – need to have more knowledge about many drugs for seizures and

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hypertensions (IV, oral, timing of use) o Drug quality issues o How readily could they be moved to periphery.

Monitoring, Evaluation and Research, Linda Bartlett, JHU/IIP

• Started with thinking about the goals of the program for the PE/E working group: o Ensure universal use of appropriate treatment at least in facilities; need more

thorough understanding of treatments that could be used in communities o Solid understanding of prevention of PE/E through calcium supplementation

• Calcium does not seem to have an adequate level of evidence for implementation in communities.

• Will identify all research gaps and classify by efficacy studies versus effectiveness studies versus implementation science. Can also discuss resources, sample sizes.

• Clinical interventions and diagnostic techniques needed for policy and advocacy (clinical interventions and diagnostic techniques)

• Barriers to magnesium sulfate • Thorough, prioritized list by need, resource and type of question; can choose key questions

that we get funding for to answer • Needs to be a definition of PE/E so we could monitor cases incidence/prevalence.

Discussion Questions and Answers Harshad prompted participants to think about how to move forward the agenda/how to prioritize and a process of working through. What consensus is needed? We know PE/E is a killer and one should use magnesium sulfate.

• There may be another question such as at what levels can magnesium sulfate be delivered, etc.

• This is part of the guidelines and WHO is looking at the evidence and are welcome to have the working group assist in updating the guidelines as well standards. We already have guidelines but just need to update them.

• If everyone disagrees about calcium will programs stop their calcium supplementation? Matthews Mathai has suggested that programs move slowly.

How can we move forward? Do we need another randomized control trial? Operational research? What guidance from the group is there?

• Need to test effectiveness of calcium before moving toward supplementation. • It’s early to initiate calcium supplementation in a program but there is still a need for some

research questions to be appropriately addressed in the short period. o How to provide calcium at the appropriate level for the population? o Does this provision benefit the women during pregnancy and in children? o Can be a long period between establishing efficacy and rolling out an intervention. In

theory this can be done in parallel. • May be an agenda for analytic work to determine under what circumstances it’s beneficial to

move an intervention forward. Need to figure out when to look at other supplements. There can be an analytic process around this using current evidence.

• Our goal should be to get the things we know already work universally out there – for now this mean magnesium sulfate and antihypertensives.

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• A small focus study in countries where the standards have been taken up successfully versus somewhere they have not to determine major barriers to uptake.

Patricia Gomez mentioned that follow-up with the small groups would occur through MCHIP. Specific people will be in touch with each group to foster discussion. MCHIP will work with the groups to move the process forward and to bring groups together at common meetings and via phone conference.

Closing Remarks Koki Agarwal, Harshad Sanghvi, and Mary Ellen Stanton (USAID)

• Mary Ellen Stanton, from the USAID MCH Bureau, thanked participants for attending the meeting and said she is excited to see the working groups move forward.

• Koki Agarwal, MCHIP Director, was amazed at how many people were interested in Monitoring, Evaluation and Research. Koki thanked the meeting organizers, Patricia and Harshad for gathering everyone together. MCHIP has identified PE/E as a priority and MCHIP is committed and eager to support the work outlined.

• Harshad thanked the presenters for pulling together presentations on a complex subject and thanked participants for volunteering for the working groups.

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Annex 1: MCHIP brief

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Annex 2: Meeting Agenda

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Annex 3: Participant List

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