Balancing the Scales- A Report on Barriers and Solutions to treat Pre-eclampsia and Eclampsia
Publication date: 2007
Balancing the ScaleS expanding treatment for pregnant Women With life-threatening hypertenSive conditionS in developing countrieS a report on Barriers and Solutions to treat pre-eclampsia & eclampsia www.engenderhealth.org Acknowledgments. 3 Executive.Summary. 4 I.Introduction. 6 II.Barriers.to.Compliance.with.International.Standards.of.Care. 10 III.The.Way.Forward:.Solutions.to.Expanding. Utilization.of.Magnesium.Sulfate. 12 References. 14 contentS ©.2007.EngenderHealth Cover.photo.credits.top.to.bottom:.A.Fiorente/EngenderHealth,.M.Tushman/EngenderHealth,.C.Svingen/EngenderHealth 3. Acknowledgments EngenderHealth.gratefully.acknowledges.the.John.D.and.Catherine.T.MacArthur. Foundation,.with.special.thanks.to.Ann.Blanc.and.Judith.Helzner.for.supporting. the.Workshop.on.Magnesium.Sulfate.for.the.Management.of.Pre-eclampsia.and. Eclampsia,.June.26–27,.2007,.which.provided.the.opportunity.to.bring.international. experts.together.to.address.this.major.public.health.issue.Special.thanks.go.to. Drs.Stephen.Kennedy.and.José.Villar.of.the.Nuffield.Department.of.Obstetrics. &.Gynaecology.at.Oxford.University.for.co-hosting.the.meeting. EngenderHealth.also.thanks.members.of.the.Technical.Advisory.Group,.who. provided.invaluable.input.to.the.meeting.content.and.attendees. Many.individuals.from.institutions.across.Africa,.Asia,.and.Latin.America.generously. shared.their.insights.on.pre-eclampsia.and.eclampsia.for.the.purposes.of.this.meeting. and.helped.create.a.road.map.for.the.journey.ahead.Although.their.names.are.too. many.to.mention,.we.are.indebted.to.them. Specific.writers.and.reviewers.of.this.report.included.Kelly.O’Hanley,.Theresa.Kim,. Katie.Tell,.and.Ana.Langer.EngenderHealth.also.thanks.Kathleen.McFarland,. Michael.Klitsch,.Tor.de.Vries,.Weronika.Murray,.and.Ariana.Souzis.for.their.diverse. contributions.to.the.final.report. October.17,.2007 acknoWledgmentS 4. Executive.Summary Giving.birth.should.be.a.time.for.celebration,.but.for.more.than.half.a.million.women. each.year—or.one.woman.every.minute—pregnancy.and.childbirth.end.in.death.and. mourning.Ninety-nine.percent.of.these.deaths.occur.in.the.developing.world,.and. tragically,.most.of.these.deaths.are.preventable. One.of.the.most.common,.yet.treatable,.causes.of.maternal.death.worldwide.is. pre-eclampsia—the.rapid.elevation.of.blood.pressure.during.pregnancy—which,.if. untreated,.can.lead.to.seizures.(eclampsia),.kidney.and.liver.damage,.and.ultimately,. death.The.World.Health.Organization.(WHO).estimates.that.at.least.16%.of. maternal.deaths.in.developing.countries.result.from.these.conditions.(UNDP/ UNFPA/WHO/World.Bank.Special.Programme,.2006).Thus,.approximately.63,000. pregnant.women.die.every.year.because.of.eclampsia.and.severe.pre-eclampsia,. which.are.also.associated.with.a.higher.risk.of.newborn.deaths. Pre-eclampsia/eclampsia.ranks.second.only.to.hemorrhage.as.a.specific,.direct. cause.of.maternal.death.In.some.countries,.such.as.Mexico,.pre-eclampsia.and. eclampsia.is.the.number.one.killer.The.risks.that.a.woman.faces.vary.greatly. depending.on.where.she.lives:.The.risk.that.a.woman.in.a.developing.country.will. die.of.pre-eclampsia/eclampsia.is.approximately.300.times.higher.than.that.for.a. woman.in.a.developed.country.While.the.use.of.magnesium.sulfate.has.become. the.mainstay.of.treatment.of.pre-eclampsia.and.eclampsia.in.the.vast.majority.of. developed.countries,.medications.such.as.diazepam.and.phenytoin.(used.in.the. treatment.of.other.types.of.seizures,.including.epilepsy).have.become.more.widely. used.in.most.other.parts.of.the.world. Several.research.trials.have.identified.magnesium.sulfate.as.the.most.effective. treatment.for.preventing.the.onset.of.deadly.seizures.In.fact,.the.maternal.mortality. rate.was.reduced.by.55%.in.the.33-country.Magpie.Trial,.which.was.conducted.in. 1995.Similarly,.in.the.Collaborative.Eclampsia.Trial.(2002),.magnesium.sulfate.was. proven.to.be.more.than.twice.as.effective.at.preventing.recurrent.seizures.as.the.two. drugs.(diazepam.and.phenytoin).that.had.been.the.drugs.of.choice.for.this.problem. in.most.countries.Treating.mothers.with.magnesium.sulfate.improved.outcomes.not. only.for.mothers,.but.for.their.babies.as.well. While.these.findings.are.compelling,.the.research.in.itself.has.not.translated.into. national.health.policies.and.clinical.practices.in.many.parts.of.the.developing.world. Mothers.continue.to.die.from.the.lack.of.magnesium.sulfate—a.safe,.effective,.and. inexpensive.drug.Today,.magnesium.sulfate.is.still.not.available.in.the.hospitals. of.many.countries,.nor.is.it.on.the.countries’.essential.drug.lists.In.some.nations,. magnesium.sulfate.is.not.even.licensed.for.sale. Based.on.the.scientific.evidence,.WHO.identified.magnesium.sulfate.as.the.most. effective.and.low-cost.medication.for.treatment.of.pre-eclampsia.and.eclampsia. (WHO,.1994).Unfortunately,.magnesium.sulfate.continues.to.be.underutilized,. especially.in.countries.where.pre-eclampsia.and.eclampsia.remains.one.of.the. main.causes.of.maternal.mortality.and.morbidity. executive Summary 5. Executive.Summary In.light.of.the.above,.EngenderHealth.brought.together.international.health. experts.to.study.and.come.to.a.consensus.on.the.key.barriers.to.the.use.of.this. life-saving.tool.and.to.develop.a.road.map.to.improve.access.and.implementation. of.magnesium.sulfate.treatment.The.Workshop.on.Magnesium.Sulfate.for.the. Management.of.Pre-eclampsia.and.Eclampsia,.held.on.June.26–27,.2007,.in. Oxford,.England,.was.conducted.in.coordination.with.a.Technical.Advisory.Group,. which.served.as.an.advisory.body.overseeing.the.preparation.and.planning.for. the.workshop.The.Technical.Advisory.Group.included.representatives.from.the. following.agencies:.Columbia.University.(The.Averting.Maternal.Death.and. Disability.Program),.EngenderHealth,.the.London.School.of.Hygiene.and.Tropical. Medicine,.UNICEF,.the.University.of.Leeds,.the.University.of.Oxford,.and.the. World.Health.Organization.Workshop.attendees.included.technical.experts,. country-level.representatives.from.Ministries.of.Health.and.public.health.services,. and.representatives.from.universities.and.international.organizations.Given.the. complexity.of.the.issues,.the.Workshop.required.a.multidisciplinary.group.of. experts.representing.diverse.experiences.and.countries.Participants.represented.the. countries.of.Ghana,.India,.Malawi,.Mexico,.Nepal,.Nigeria,.Switzerland,.Thailand,. the.United.Kingdom,.and.the.United.States. This.historic.gathering.of.global.public.health.experts.identified.the.primary.barriers. to.expanding.access.to.magnesium.sulfate.in.developing.countries,.including: • lack of national priority and guidelines.In.countries.like.Nigeria,.Uganda,. and.Pakistan,.guidelines.mandating.magnesium.sulfate.use.do.not.exist,.and. only.about.half.of.the.world’s.countries.include.magnesium.sulfate.on.their. national.list.of.“essential.drugs.”. . •.lack of education and training.Many.clinicians.remain.unfamiliar.with. the.safety.and.effectiveness.of.magnesium.sulfate.and.continue.to.rely.on. other,.less.effective.and.riskier.drugs.Education.and.training.on.the.scientific. validity.and.treatment.protocols.are.needed. . •.Supply Shortage. Relative.to.other.health.conditions,.pre-eclampsia.and. eclampsia.affect.a.small.population.In.addition,.magnesium.sulfate.is. relatively.inexpensive.In.combination,.these.factors.leave.little.or.no. incentive.for.pharmaceutical.companies.to.make.magnesium.sulfate.more. widely.available. Based.on.these.conclusions,.EngenderHealth.and.the.University.of.Oxford.have. developed.a.“Call.to.Action”.that.calls.on.policy.makers.and.ministers.of.health.to. make.pre-eclampsia.and.eclampsia.a.higher.priority.and.to.set.national.guidelines. for.treatment.and.care,.based.on.WHO.guidelines.It.also.urges.decision.makers. and.international.and.national.health.organizations.and.agencies.to.help.make. magnesium.sulfate.more.available.and.affordable,.in.part.by.empowering.local. clinicians.with.education.and.training. 6. I.Introduction the cost of childbirth For.most.women.and.their.families,.giving.birth.should.be.a.time.for.celebration,. but.for.more.than.half.a.million.women.each.year—or.one.woman.every.minute— pregnancy.and.childbirth.end.in.death.and.mourning.(UNFPA,.2000).Ninety-nine. percent.of.maternal.deaths.occur.in.the.developing.world,.and.most.of.these.deaths. are.preventable.The.risk.of.death.and.disability.resulting.from.reproduction.reflects. the.enormous.disparities.in.maternal.health.care.between.industrialized.and.poor. nations.Indeed,.the.risk.of.a.woman’s.dying.as.a.result.of.pregnancy.or.childbirth. during.her.lifetime.is.about.one.in.seven.in.Afghanistan.or.Sierra.Leone,.while.it.is. only.one.in.30,000.in.Sweden.(Lawn,.Cousens,.&.Zupan,.2005). Although.the.reduction.of.maternal.mortality.was.adopted.by.the.global. development.community.as.one.of.the.Millennium.Development.Goals.and.is.a. stated.target.of.many.countries.and.international.institutions,.pregnancy-related. deaths.have.fallen.little.in.most.low-resource.countries.over.the.past.decades. The.lack.of.success.in.improving.pregnancy.outcomes.has.been.a.result.of.failing. health.systems,.as.well.as.of.insufficient.political,.financial,.and.social.commitment. to.the.issue. What are pre-eclampsia and eclampsia? Pre-eclampsia.is.a.rapidly.progressive.condition.that.can.lead.to.stroke,.kidney.or. liver.damage,.blood-clotting.problems,.and.pulmonary.edema.(fluid.in.the.lungs). The.diagnosis.of.pre-eclampsia.is.based.primarily.on.the.presence.of.hypertension. and.protein.in.the.urine.during.the.latter.stages.of.pregnancy.Eclampsia.is.defined. as.the.development.of.convulsions.or.coma.in.a.woman.with.pre-eclampsia.Pre- eclampsia.and.eclampsia.occur.much.more.commonly.in.first-time.pregnancies.and. appear.typically.with.minimal.or.no.warning.The.antenatal.onset.of.pre-eclampsia. and.eclampsia.is,.by.definition,.after.the.20th.week.of.pregnancy.However,.up.to. 25%.of.pre-eclampsia.and.eclampsia.cases.occur.after.delivery—usually.within.48. hours.postpartum.Some.women.with.pre-eclampsia.develop.eclamptic.seizures. Pre-eclampsia.and.eclampsia.can.also.result.in.perinatal.deaths.While.many.theories. have.been.suggested.to.explain.the.etiology.of.pre-eclampsia.and.eclampsia,.to.date. no.single.or.unifying.explanation.of.the.cause.exists.Unfortunately,.pre-eclampsia.is. not.preventable,.nor.is.its.onset.accurately.predictable. latest data for pre-eclampsia and eclampsia The.World.Health.Organization.(WHO).identifies.the.leading.causes.of.maternal. mortality.worldwide.as:.hemorrhage.(25%),.indirect.causes.(20%),.infections.(15%),. unsafe.abortion.(13%),.pre-eclampsia/eclampsia.(12%),.obstructed.labor.(8%),.and. other.direct.causes.(8%).Pre-eclampsia/eclampsia.ranks.second.only.to.hemorrhage. as.a.specific,.direct.cause.of.maternal.mortality.However,.these.global.averages. hide.important.variations.among.countries.For.instance,.in.Mexico,.pre-eclampsia/ eclampsia.is.the.number.one.cause.of.maternal.death.(Lozano.et.al.,.2005).In.2002,. there.were.approximately.4,152,000.cases.of.pre-eclampsia.and.eclampsia.that. resulted.in.63,000.deaths.worldwide.(WHO,.2005). i. introduction 7. I.Introduction the price of pre-eclampsia and eclampsia: how it affects “us” vs. “them” The.cumulative.risks.from.pre-eclampsia.and.eclampsia.are.many.times.higher.for.a. woman.in.a.developing.country.than.for.a.woman.in.a.developed.country.A.woman. in.a.developing.country.is.seven times more.likely.to.develop.pre-eclampsia.If.she. develops.pre-eclampsia,.she.is.three times.more.likely.to.progress.to.eclampsia.Should. she.develop.eclampsia,.she.is.up.to.14 times.more.likely.to.die.of.eclampsia—even. in.hospital.settings.Taken.together,.the.risk.of.dying.of.pre-eclampsia.and.eclampsia. is.approximately.300 times higher.for.a.woman.in.a.developing.country.than.for.a. woman.in.a.developed.country. Incidence of Pre-eclampsia The.incidence.of.pre-eclampsia,.the.precursor.to.eclampsia,.varies.greatly.worldwide. WHO.estimates.the.incidence.(or.number.of.new.cases).of.pre-eclampsia.to.be.seven. times.higher.in.developing.countries.(2.8%.of.live.births).than.in.developed.countries. (0.4%).(Dolea.et.al.,.2003). Progression of Pre-eclampsia to Eclampsia Only.a.relatively.small.proportion.of.all.women.with.pre-eclampsia.progress.to.the. more.potentially.deadly.eclampsia.However,.once.again,.a.pre-eclamptic.woman. in.a.developing.country.is.three.times.more.likely.to.progress.to.eclampsia.than.a. woman.in.a.developed.country.The.WHO.estimates.that.eclampsia.develops.in. 2.3%.of.pre-eclamptic.women.in.the.developing.world,.compared.with.0.8%.of. pre-eclampsia.cases.in.developed.countries. Challenges to Defining the Problem: Variations in Death Rates from Eclampsia Reliable.statistics.about.women.dying.due.to.eclampsia.are.difficult.to.obtain.because. of.the.poor.quality.of.vital.statistics.registration.systems.and.hospital.records.in.many. developing.countries.In.addition,.a.sizable.number.of.deliveries.take.place.at.home,. and.thus.there.are.no.records.at.all.for.these.births.Therefore,.data.on.women.who. die.from.eclampsia.are.only.available.from.a.limited.number.of.countries.(see.Table.1,. below).Nevertheless,.it.is.clear.that.the.case.fatality.rates.for.eclampsia.vary.greatly. across.countries,.with.the.risk.of.death.from.eclampsia.being.much.higher. in.developing.countries.than.in.developed.ones. table 1: case fatality rates for eclampsia in select countries Source:.World.Health.Organization.2003.Evidence.and.information.for.policy. Geneva.These.data.are.drawn.exclusively.from.hospital-based.studies. country caSe fatality rate year(S) . Burkina.Faso. 15.7%. 1992–1995 . Niger. 5.9%. 1997 . South.Africa. 21.2%. 1994–1995 . South.Africa. 26.3%. 1996–1997 . Peru. 8.0%. 1991–1997 . Thailand. 3.3%. 1988–1997 . United.Kingdom. 1.8%. 1992 8. I.Introduction magnesium Sulfate: the evidence-Based Solution While.there.is.no.cure.for.pre-eclampsia.and.eclampsia,.treatment.measures.can. prevent.and/or.reduce.maternal.and.perinatal.death.and.disability.The.currently. prescribed.management.of.pre-eclampsia.and.eclampsia.originated.in.the.early. 1900s.In.1925,.Lazard.published.a.preliminary.report.in.the.American Journal of Obstetrics and Gynecology.describing.the.effectiveness.of.magnesium.sulfate. for.treating.pre-eclampsia.and.eclampsia.(Lazard,.1925).The.use.of.magnesium. sulfate.went.on.to.become.the.standard.treatment.of.pre-eclampsia.and.eclampsia. in.the.United.States.The.results.did.not.translate.globally,.and.other,.less-effective. medications,.such.as.diazepam.and.phenytoin.(used.in.the.treatment.of.other.types. of.seizures,.including.epilepsy),.were.more.widely.used.in.other.countries.to.treat. pre-eclampsia/eclampsia. Evidence of Effectiveness Treating Eclampsia In.1995,.more.research.confirmed.the.superiority.of.magnesium.sulfate.for.the. treatment.of.eclamptic.seizures.compared.to.other.medications.The.Collaborative. Eclampsia.Trial.compared.the.relative.effectiveness.of.the.three.most.popular. treatments.(magnesium.sulfate,.diazepam,.and.phenytoin).for.the.treatment. of.eclampsia.(Eclampsia.Trial.Collaborative.Group,.1995).Women.treated.with. magnesium.sulfate.had.a.52%.and.67%.lower.recurrence.of.convulsions.than. those.treated.with.diazepam.and.phenytoin,.respectively. During.the.Collaborative.Eclampsia.Trial,.treatment.packs.were.prepared.for.the. clinicians.to.treat.women.participating.in.the.study.The.packs.contained.magnesium. sulfate.(prepackaged.for.recommended.standard.dosing),.calcium.gluconate. (an.antidote.for.toxicity.from.magnesium.sulfate),.supplies.for.intravenous.and. intramuscular.administration,.record.sheets.to.record.clinical.monitoring.findings,. and.a.protocol.sheet.that.also.included.guidelines.for.other.aspects.of.relevant.care. Evidence of Effectiveness Treating Pre-eclampsia Although.the.Collaborative.Eclampsia.Trial.provided.compelling.evidence. about.the.superiority.of.magnesium.sulfate.for.treatment.of.eclamptic.seizures,. questions.remained.about.the.effectiveness.of.magnesium.sulfate.for.the.treatment. of.pre-eclampsia. In.2002,.a.randomized,.placebo-controlled.study.enrolled.more.than.10,000. women.from.33.countries.to.address.this.issue.(Altman.et.al.,.2002).Known.as. the.Magpie.Trial,.the.landmark.study.enrolled.12.times.more.women.than.any. previous.pre-eclampsia.study.to.compare.the.efficacy.of.magnesium.sulfate.to. placebo.The.Magpie.Trial.determined.that.when.magnesium.sulfate.was.given.to. women.with.pre-eclampsia,.it.lowered.the.chance.of.seizure.by.58%.Following.the. Magpie.Trial,.magnesium.sulfate.was.placed.on.the.WHO.essential.drugs.list,.and. as.a.result,.many.countries.began.full.use.of.the.drug,.such.as.the.United.Kingdom. “no woman in this day and age should die from eclampsia simply because of where she happens to live. it’s a tragedy, because we have an effective, low-cost, and safe solution.” – dr. ana langer, engenderhealth the [eclampsia] treatment packs are “a simple, relatively cheap, and effective way of ensuring that magnesium sulfate is always readily at hand. in developing countries, the problem is the familiar one of maintaining a regular supply of any essential drug. in developed countries, the issue is getting rapid access to a drug that is only rarely required.” – dr. leila duley, chair, obstetric epidemiology, university of leeds. 9. I.Introduction Improving Neonatal Outcomes Perinatal.outcomes.for.women.treated.with.magnesium.sulfate.for.pre-eclampsia. and.eclampsia.have.been.studied.in.recent.years.Cochrane.Review.articles.reported. better.outcomes.for.babies.of.mothers.who.received.magnesium.sulfate.for. eclampsia.than.for.those.who.received.diazepam.or.phenytoin.Specifically,.the.vigor. of.the.babies.(five.minutes.after.birth).was.greater.and.the.chances.of.a.long.hospital. stay.in.an.intensive.care.unit.were.lower.in.the.magnesium.sulphate–treated.group. than.in.the.diazepam-treated.group.Similarly,.maternal.magnesium.sulfate.treatment. was.associated.with.fewer.neonatal.admissions.to.a.special.care.unit,.a.shorter. duration.of.stay.(in.days).in.the.neonatal.care.unit,.and.fewer.neonatal.deaths.when. compared.with.maternal.treatment.with.phenytoin.(Duley.et.al.,.2003a;.Duley.et.al.,. 2003b). Current Clinical Guidelines The.positive.research.data.from.the.Magpie.Trial.led.institutions.including.the.WHO,. the.American.College.of.Obstetricians.and.Gynecologists.(ACOG),.and.the.Royal. College.of.Obstetricians.and.Gynaecologists.(RCOG).to.recommend.the.use.of. magnesium.sulfate.as.the.first-line.treatment.for.pre-eclampsia.and.eclampsia.Their. recommendations.specify.correct.dosing.and.administration.and.also.emphasize.the. importance.of.monitoring.to.ensure.safety. Recommendations.for.the.care.of.a.woman.with.pre-eclampsia/eclampsia.extend. beyond.simply.the.proper.administration.of.magnesium.sulfate.Current.guidelines. address.appropriate.laboratory.tests.for.blood.count.and.liver.and.kidney.function. RCOG.and.ACOG.also.specify.the.need.for.treatment.of.severely.elevated.blood. pressure.with.an.antihypertensive.medication.to.prevent.nonseizure.complications. For.more.specific.guidelines.on.the.management.of.pre-eclampsia.and.eclampsia,. visit.WHO.at.www.who.int/,.ACOG.atd.www.acog.org,.or.RCOG.at. www.rcog.org.uk. 10. II.Barriers.to.Compliance.with.International.Standards.of.Care transforming evidence to practice The.presence.of.magnesium.sulfate.within.a.country.and.distribution.of.the.drug. to.facilities.are.basic.prerequisites.for.complying.with.international.guidelines.for. pre-eclampsia.and.eclampsia.care.Despite.compelling.data.about.magnesium. sulfate.as.the.first.choice.for.treatment,.the.drug.remains.inaccessible.to.millions.of. women.in.developing.countries.For.example,.in.the.United.Kingdom,.since.1991,. the.use.of.magnesium.sulfate.in.cases.of.pre-eclampsia.rose.from.2%.to.100%. By.contrast,.in.many.developing.countries,.magnesium.sulfate.is.still.unavailable.or. underutilized,.and.other.anti-seizure.medications.continue.to.be.used.preferentially. over.magnesium.sulfate.These.facts.indicate.that.although.research.findings.are. essential.to.improve.clinical.practices,.they.are.not.sufficient.to.change.health.policies. and.routine.clinical.care. Although.some.studies.have.attempted.to.understand.why.this.evidence.has.not. translated.into.changes.in.practice,.there.had.never.been.a.specific.forum.to.address. this.issue.head.on.The.Workshop.on.Magnesium.Sulfate.for.the.Management.of. Pre-eclampsia.and.Eclampsia,.held.in.June.2007.in.Oxford,.was.conducted.to.identify. the.key.barriers.to.expanding.access.to.magnesium.sulfate,.including.country- specific.barriers,.and.to.develop.solutions.to.address.them.The.experts.attending. the.meeting.identified.the.following.key.barriers.to.translating.knowledge.about. magnesium.sulfate.into.policies.and.practice. key Barriers Lack of National Priority and Guidelines In.countries.such.as.Nigeria.and.Pakistan,.national.guidelines.mandating.magnesium. sulfate.use.do.not.exist.And.only.about.half.of.all.countries.in.the.world.include. magnesium.sulfate.on.their.national.list.of.“essential.drugs.”.Where.national. guidelines.do.exist,.facilities.and.clinicians.are.sometimes.under.no.obligation.to. follow.them.In.many.cases,.each.facility.develops.and.follows.its.own.policies. . Lack of Education and Training Many.clinicians.are.unfamiliar.with.the.safety.and.effectiveness.of.magnesium. sulfate.and.continue.to.rely.on.other,.less-effective.and.riskier.drugs.Health.care. providers.and.administrators.may.be.reluctant.to.adopt.a.practice.with.which.they. have.had.little.experience.or.one.that.requires.intensive.monitoring.for.a.condition. that.is.relatively.infrequent. In.addition,.few.clinicians.or.policy.makers.in.developing. countries.are.aware.of.the.concept.of.evidence-based.medicine.or.know.about.the. findings.from.the.Magpie.Trial.In.some.countries,.experts.report.that.the.utilization. of.magnesium.sulfate.is.viewed.as.being.appropriate.only.at.highest.functional. facilities.(such.as.facilities.with.an.intensive.care.unit).because.of.the.misperception. that.women.receiving.magnesium.sulfate.require.very.complex.monitoring. Supply Shortage Relative.to.other.health.conditions,.pre-eclampsia.and.eclampsia.affect.a.small. population.In.addition,.the.drug.itself.is.relatively.inexpensive.In.combination,.these. factors.leave.little.or.no.incentive.for.pharmaceutical.companies.to.make.magnesium. sulfate.more.widely.available. ii. BarrierS to compliance With international StandardS of care 11. II.Barriers.to.Compliance.with.International.Standards.of.Care Lack of Comprehensive, Country-by-Country Data Solid.data.about.the.availability.of.magnesium.sulfate.are.generally.lacking.in.many. countries,.and.the.data.that.do.exist.often.present.a.challenging.picture.For.example,. 2003.national.surveys.in.Ghana.and.Rwanda.reported.that.only.7%.and.25%.of. facilities.offering.delivery.services.stocked.magnesium.sulfate.(respectively).In.2005,. the.drug.was.entirely.absent.from.a.teaching.hospital.in.Nigeria.Sevene.et.al.(2005). conducted.a.case.study.in.Mozambique.and.Zimbabwe.to.examine.the.reasons.why. magnesium.sulfate.continues.to.be.unavailable.in.these.countries.The.factors.identified. included:.insufficient.demand.for.the.drug.by.physicians;.poor.communication.between. clinicians.and.pharmacists;.complex.mechanisms.of.drug.approval,.acquisition,.and. distribution;.priority.given.to.drugs.used.at.all.levels.of.the.health.system;.and.limited. drug.budgets. Financial Cost The.cost.of.magnesium.sulfate.and.the.hospital.care.involved.with.providing.it. were.seen.as.an.impediment.to.its.use.in.some.countries.The.problem.of.cost.was. reflected.in.the.discrepancies.between.private.and.public.facilities.in.their.ability.to. stock.magnesium.sulfate.The.cost.of.magnesium.sulfate.also.differs.depending.on. the.country.While.generally.inexpensive.across.most.countries,.it.is.more.expensive. in.places.such.as.in.Nigeria,.than.other,.less.favorable.drugs. Weak Health Systems Without.a.stable.health.system,.any.intervention,.including.one.that.is.relatively.easy. to.administer.with.clinical.training,.will.not.succeed.It.is.critical.to.ensure.that.any. training.or.program.with.magnesium.sulfate.is.offered.in.the.context.of.a.functional. health.system,.where.providers.are.able.to.participate.in.job.training.and.adopt.new. practices,.where.the.procurement.and.distribution.systems.are.effective,.where.norms. and.institutional.quality.protocols.are.in.place,.and.where.facilities.are.reasonably.well- equipped.It.is.also.important.that.interventions.like.magnesium.sulfate.are.provided.as. part.of.a.package.of.emergency.obstetric.care.and.in.the.context.of.a.comprehensive. reproductive.health.approach.that.addresses.women’s.inextricably.linked.needs,. including.family.planning. Dr.Bissallah.Ahmed.Ekele,.Professor.and. Chair.of.the.Department.of.Obstetrics. and.Gynecology.at.Usmanu.Danfodiyo. University,.recounted.that.when.he. graduated.from.medical.school,.he.knew.far. more.about.the.so-called.“lytic.cocktail”—. a.potentially.deadly.treatment—than.about. magnesium.sulfate.for.the.management.of. pre-eclampsia.and.eclampsia.In.his.clinical. textbooks,.where.magnesium.sulfate.was. mentioned,.providers.were.advised.to.use. the.drug.with.discouragingly.great.caution,. due.to.the.various.myths.associated.with. its.use.The.drug.diazepam.has.also.been. very.popular.in.the.management.of.pre- eclampsia.and.eclampsia.in.Nigeria,.despite. the.proven.high.recurrence.of.eclamptic. fits.associated.with.the.drug.Similar.to. other.countries,.provider.knowledge.of.and. training.about.magnesium.sulfate.is.very. limited.And.the.cost.is.prohibitively.high. compared.with.other,.less.favorable.drugs. Also,.in.many.communities,.the.culture. demands.that.women.deliver.at.home.or.at. their.parents’.house,.which.prohibits.women. from.accessing.life-saving.medical.care.in. a.timely.manner. overcoming harmful practiceS in nigeria 12. III.The.Way.Forward:.Solutions.to.Expanding.Utilization.of.Magnesium.Sulfate Based.on.these.conclusions,.EngenderHealth.and.the.University.of.Oxford.developed. a.“Call.to.Action”.that.calls.on.policy.makers.and.ministers.of.health.to.make.pre- eclampsia.and.eclampsia.a.higher.priority.and.to.set.national.guidelines.for.treatment. and.care.based.on.WHO.guidelines.It.also.urges.decision.makers.and.international. and.national.health.organizations.and.agencies.to.help.make.magnesium.sulfate. more.available.and.affordable,.in.part.by.empowering.local.clinicians.with.education. and.training.The.recommendations.for.interventions.to.expand.the.use.of. magnesium.sulfate.are:. Ensure Widespread Availability of Eclampsia Treatment Packs One.specific.and.urgently.needed.step.is.to.promote.the.use.of.“eclampsia. treatment.packs”.(such.as.those.used.in.the.Eclampsia.Collaborative.Trial).to. ensure.ready.access.and.appropriate.utilization.of.the.drug.in.all.facilities.offering. delivery.services.and.to.increase.the.likelihood.of.the.drug’s.correct.and.safe.use. The.introduction.of.emergency.packs.could.serve.as.a.training.aid.to.update.key. health.professionals.about.current.clinical.guidelines.for.management.of. pre-eclampsia.and.eclampsia. Expand Training and Education to All Health Professionals All.health.professionals.(including.family.and.emergency.room.physicians,. anesthetists,.nurses,.midwives,.medical.officers,.and.pharmacists).need.to.be. appropriately.trained.in.the.care.of.women.with.eclampsia.and.severe.pre-eclampsia,. including.the.use.of.magnesium.sulfate. Increase Political Commitment to Address Pre-eclampsia/Eclampsia, in Country and Globally All.stakeholders.concerned.about.women’s.health.are.urged.to.take.measures.to. prevent.deaths.due.to.pre-eclampsia.and.eclampsia.This.would.include.working.to:. • Add.magnesium.sulfate.to.essential.drug.lists.and.ensure.registration,. universal.availability,.and.appropriate.use.in.all.countries. • Develop.country-specific.standards.of.care.drawing.from.WHO’s.guidelines. and.best.practices.to.share.with.national.and.international.colleagues.and. organizations. • Obtain.local.support.and.identify.local.champions,.such.as.health.care. providers.and.politicians. Disseminate Research to Advocate for Increased Utilization and Access Various.champions.for.the.issue,.such.as.researchers.or.professional.organizations,. can.bring.the.results.of.their.research.to.a.wider.audience,.such.as.publishing. articles.that.call.for.updating.clinical.practices.in.national.or.regional.journals.The. information.could.then.be.used.to.convince.central.health.authorities.and.hospital. administrators.to.make.changes.in.clinical.practices.Estimating.the.cost.savings.from. the.use.of.magnesium.sulfate.resulting.in.shorter.maternal.and.newborn.hospital. stays.would.represent.a.powerful.advocacy.tool.to.influence.local.and.national. policy.makers. iii. the Way forWard: SolutionS to expanding utilization of magneSium Sulfate We have moved from: “evidence from both developed and developing countries suggests that deaths associated with hypertensive disorders of pregnancy are the most difficult to prevent” to “we have cost-effective interventions that have been proven to solve a significant proportion of the mortality from eclampsia. We now need the resources to take those interventions to women who need it most.” – dr. harshad Sanghvi, Jhpiego 13. III.The.Way.Forward:.Solutions.to.Expanding.Utilization.of.Magnesium.Sulfate Conduct Country-Specific Research Each.country’s.pharmaceutical.situation,.political.environment,.and.health.care.system. are.unique.Data.collected.about.a.country.in.one.region.often.cannot.be.generalized. to.other.contexts.For.the.purposes.of.planning.specific.interventions,.data.must. be.obtained.on.a.country-by-country.basis.in.order.to.develop.context-appropriate. strategies.for.expanding.magnesium.sulfate.availability.and.utilization.The.types.of. local.information.that.are.needed.include:.maternal.morbidity.and.mortality.resulting. from.pre-eclampsia/eclampsia,.legal.status.of.magnesium.sulfate.and.presence.on. essential.drug.list,.potential.for.political.support.for.health.policy.change,.and.current. practices.in.management.of.pre-eclampsia.and.eclampsia.The.desire.for.a.complete. data.set.for.each.country.must.be.weighed.against.the.costs,.length.of.time.needed,. and.reliability.of.the.data.collection. . The.opportunities.for.reducing.maternal.and.perinatal.morbidity.and.mortality.from. pre-eclampsia.and.eclampsia.are.extraordinary.Magnesium.sulfate.is.a.solution.with. proven.effectiveness.and.safety,.and.yet.it.still.eludes.thousands.of.women.who.die. needlessly.each.year.Although.the.use.of.magnesium.sulfate.has.lagged.in.many. developing.countries,.resources.to.expand.its.availability.and.use.also.exist:.Actions. by.international.organizations,.championing.by.highly.regarded.local.clinicians,.and. the.support.of.local.policy.makers.can.all.help.make.magnesium.sulfate.the.leading. treatment.to.save.women’s.lives. “When you’re dealing with a condition that rarely results in death in countries like the united States but persists as the number one killer of pregnant women in other countries, including mexico, then the problem is not the limit of modern medicine, but one of lack of access, clinicians’ training, and political will.” – dr. ana langer, engenderhealth mainStreaming the uSe of magneSium Sulfate in mexico Dr.Ricardo.David.Muñoz.Soto,.from.the. Ministry.of.Health,.and.Dr.Sandra.García,. from.the.Population.Council,.Mexico,. shared.the.situation.of.magnesium.sulfate. in.Mexico.Pre-eclampsia.and.eclampsia. is.the.leading.cause.of.maternal.death.in. Mexico,.with.magnesium.sulfate.officially. listed.as.the.recommended.standard. of.care.for.this.problem.The.drug.is. inexpensive,.costing.less.than.$5.per. patient,.and.it.is.widely.available,.with. very.few.reported.side.effects.Despite. these.factors,.magnesium.sulfate.is.not. widely.used.in.the.country.Key.barriers. include:.insufficient.medical.curricula.about. pre-eclampsia.and.eclampsia;.difficult. packaging.of.magnesium.sulfate.(i.e.,. magnesium.sulfate.coming.in.1,000.and. 500.ml.packs,.when.the.needed.amount. is.250ml);.less-effective.drugs,.such.as. phenytoin,.coming.prepackaged.and.thus. being.easier.to.administer;.and.insufficient. medical.training,.with.providers.failing.to. detect.the.symptoms.of.mild.pre-eclampsia. and.lacking.confidence.to.administer. magnesium.sulfate. In.response,.the.Ministry.of.Health.has. pledged.its.commitment.to.making. magnesium.sulfate.more.widely.utilized. for.the.treatment.of.pre-eclampsia.and. eclampsia.In.2005,.intensive.emergency. obstetric.care.workshops.held.in.12.states. included.pre-eclampsia.and.eclampsia.and. its.management.with.magnesium.sulfate. The.Ministry.of.Health.and.the.Population. Council.are.partnering.to.address.the. barriers.to.use.of.magnesium.sulfate.and. to.test.interventions.aimed.at.increasing. utilization. 14. References Aaserud,.M.,.Lewin,.S.,.Innvaer,.S.,.et.al.2005.Translating.research.into.policy.and.practice. in.developing.countries:.a.case.study.of.magnesium.sulphate.for.pre-eclampsia.BMC.Health. Services.Research.5:68. Altman,.D.,.Carroli,.G.,.Duley,.L.,.et.al.2002.Do.women.with.pre-eclampsia,.and.their.babies,. benefit.from.magnesium.sulfate?.The.Magpie.Trial:.a.randomized.placebo-controlled.trial. Lancet.359(9321):1877–1890. American.College.of.Obstetricians.and.Gynecologists.(ACOG).2002.Diagnosis.and. management.of.pre-eclampsia.and.eclampsia.ACOG.Practice.Bulletin.No.33. Washington,.DC. Conde-Agudelo,.A.,.Vilar,.J.,.and.Lindheimer,.M.2004.World.Health.Organization.systematic. review.of.screening.tests.for.pre-eclampsia.Obstetrics.&.Gynecology.104:1367–1391. Dolea,.C.,.and.AbouZahr,.C.2003.Global.burden.of.hypertensive.disorders.of.pregnancy. in.the.year.2000.Global.Burden.of.Diseases.2000.Working.Paper.Geneva:.World.Health. Organization.(WHO). Duley,.L.1996.Magnesium.sulphate.regimens.for.women.with.eclampsia:.messages.from.the. Collaborative.Eclampsia.Trial.British.Journal.of.Obstetrics.&.Gynaecology.103:103–105. Duley,.L.,.and.Henderson-Smart,.D.2003a.Magnesium.sulphate.versus.diazepam.for. eclampsia.Cochrane.Database.of.Systematic.Reviews.4,.Art.No.CD000127. Duley,.L.,.and.Henderson-Smart,.D.2003b.Magnesium.sulphate.versus.phenytoin.for. eclampsia.Cochrane.Database.of.Systematic.Reviews.4,.Art.No.CD000128. The.Eclampsia.Trial.Collaborative.Group.1995.Which.anticonvulsant.for.women.with. eclampsia?.Evidence.from.the.Collaborative.Eclampsia.Trial.Lancet.345(8963):1455–1463. Gulmezoglu,.A.,.Langer,.A.,.Piaggio,.G.,.et.al.2007.Cluster.randomized.trial.of.an.active,. multifaceted.educational.intervention.based.on.the.WHO.Reproductive.Health.Library.to. improve.obstetric.practices.British.Journal.of.Obstetrics.&.Gynaecology.114(1):16–23. Katz,.V.,.Farmer,.R.,.and.Kuller,.J.2000.Pre-eclampsia.into.eclampsia:.toward.a.new.paradigm. American.Journal.of.Obstetrics.&.Gynecology.182(6):1389–1396. Lawn,.J.E.,.Cousens,.S.,.and.Zupan,.J.2005.4.million.neonatal.deaths:.When?.Where?.Why?. Lancet;.365:891–900. Lozano,.R.,.Torres,.L.,.Larra,.J.,.et.al.2005.WHO.Family.of.International.Classifications. Network.Meeting.http://www.who.int/classifications/apps/icd/meetings/tokyomeeting/P1-4 %20Lozano%20%20Misclassification%20of%20maternal%20deaths%20in%20Mexico.pdf. Lazard,.E.1925.A.preliminary.report.on.the.intravenous.use.of.magnesium.sulfate.in.puerperal. eclampsia.American.Journal.of.Obstetrics.&.Gynecology.9:178–188. referenceS 15. References MacGillivray,.I.,.McCaw-Binns,.A.,.Ashley,.D.,.et.al.2004.Strategies.to.prevent.eclampsia.in.a. developing.country:.2.Use.of.maternal.pictorial.card.International.Journal.of.Gynecology. &.Obstetrics.87(3):295–300. McCaw-Binns,.A.,.Ashley,.D.,.Knight,.L.,.et.al.2004.Strategies.to.prevent.eclampsia.in. a.developing.country:.1.Reorganization.of.maternity.services.International.Journal.of. Gynecology.&.Obstetrics.87(3):286–294. Royal.College.of.Obstetricians.and.Gynaecologists.(RCOG).2006.The.management.of.severe. pre-eclampsia.RCOG.Guideline.No.10(A).London. Sevene,.E.,.Lewin,.S.,.Mariano,.A.,.et.al.2005.System.and.market.failures:.the.unavailability. of.magnesium.sulphate.for.the.treatment.of.eclampsia.and.pre-eclampsia.in.Mozambique.and. Zimbabwe.British.Medical.Journal.331(7519):765–769. Sibai,.B.2005.Diagnosis,.prevention,.and.management.of.eclampsia.American.Journal.of. Obstetrics.&.Gynecology.105(2):402–410. Simon,.J.,.Gray,.A.,.and.Duley,.L.2006.Cost-effectiveness.of.prophylactic.magnesium.sulphate. for.9996.women.with.pre-eclampsia.from.33.countries:.economic.evaluation.of.the.Magpie. Trial.British.Journal.of.Obstetrics.&.Gynaecology.113(2):144–151. Thorp.J.2007.O’,.evidence-based.medicine—where.is.your.effectiveness?.British.Journal.of. Obstetrics.&.Gynaecology.114(1):1–2. UNDP/UNFPA/WHO/World.Bank.Special.Programme.of.Research,.Development,.and. Research.Training.in.Human.Reproduction.Khan,.K.,.Wojdyla,.D.,.Say,.L.,.et.al.2006.WHO. analysis.of.causes.of.maternal.death:.a.systematic.review.Lancet.DOI:10.1016/S0140-6736. (06)68397–68399. United.Nations.2007.Millennium.development.goals:.2007.progress.report.Accessible.at:. http://mdgs.un.org/unsd/mdg/default.aspx. United.Nations.Population.Fund.(UNFPA).2000.The.state.of.the.world.population.2000:. Lives.together,.worlds.apart.New.York.www.unfpa.org/swp/2000/english/ch01.html. Woelk,.G.,.Daniels,.K.,.Lewin,.S.,.et.al.Forthcoming.Research.into.policy:.Lessons. learned.from.introducing.magnesium.sulphate.and.controlling.malaria.in.three.southern. African.countries. . World.Health.Organization.(WHO).1994.Mother-baby.package:.Implementing.safe. motherhood.in.countries.Geneva. WHO.2005.The.world.health.report:.2005:.make.every.mother.and.child.safe.Geneva. WHO.No.date.Service.availability.mapper.Accessible.at:. www.who.int/healthinfo/sam/en/index.html.
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