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Prevention of Prematurity andStillbirth - Epidemiology, Evidence,and ResearchJames A. Litch, MD, DTMHDirector, Perinatal I...
Outline•   Millennium Development Goals (MDGs) progress•   Definitions•   Epidemiology•   What we know - Evidence review f...
Millennium  Development  Goals (MDGs)Global <5 child mortality rate hasdeclined by a third, from 89 deathsper 1,000 live b...
Millennium Development Goals (MDGs)In developing regions, maternalmortality ratio dropped by 34%between 1990 and 2008, fro...
ConnectedMNCH OutcomesConnected MNCH OutcomesRequire a New, Interdisciplinary ApproachRequire an Interdisciplinary Approac...
Definitions
Born Too Soon Report   What is preterm birth?                                                       erm                   ...
What is stillbirth?      • Classification for most LMIC is a birthweight of at least        1000 g or a gestational age of...
Epidemiology
Major Causes of Under-5 Deaths Globally       Cause of Mortality                                 Annual <5                ...
Changes inCauses ofNewborn Deaths
Born Too Soon ReportFirst ever national estimates of preterm birth for 192countries – where are the highest rates?        ...
Born Too Soon Report  Preterm births – where are the biggest numbers?                                                     ...
Preterm Births by Gestational Age and Region for2010                                        • 75% of preterm              ...
Causes of Death Due to Preterm BirthUnderlying Pathology          Cause of DeathLung immaturity               Hypoxia     ...
Challenges for Preterm Prevention: MultipleSocial, Biological, and Clinical Risk Factors•   Chorioamnionitis           •  ...
Country variation in stillbirth rates                                                                                     ...
Stillbirths during labor – 1.2 million a yearSource: The Lancet’s Stillbirths Series steering committee. Stillbirths: Wher...
Causes of stillbirths          Major causes:                1. Childbirth complications                2. Maternal infecti...
What we do know –Evidence for Interventions
2010 Global Report on Preterm Birth & Stillbirth• Identified evidence-based interventions to preventpreterm birth and stil...
Summary of assessments for INTRAPARTUM preterm birth andstillbirth interventions (based on GRADE system)
Quality evidence and strong recommendation for LMICs to    reduce the burden of preterm birthPrevention of preterm birth  ...
Estimated Lives Saved of Premature Babies in Settingswith Universal Coverage of Basic Interventions (withoutNICU)520,000 l...
Born Too Soon ReportQuality evidence and strong recommendation for LMICs toreduce the burden of stillbirthPrevention of an...
Modeling reduction in stillbirth     10 evidence-based interventions           Interventions considered in the model      ...
What we know about what works?
Born Too Soon Report Potential for lives saved through steroid injections for women in preterm labor Respiratory complicat...
Born Too Soon ReportPotential for lives saved through continuous skin-to-skin careBaby is tied skin to skin with mother 24...
What We Want to Know -current research efforts
Missed delivery opportunities to reach pretermbabies with essential interventions              Information Gap         Ava...
Thank youGlobal Alliance for the Prevention ofPrematurity and Stillbirth (GAPPS) leadsa collaborative, global effort to in...
Highly cost effective   • Childbirth care cost analysis   • Cost per maternal death prevented is US$54,350   • Counting ne...
10                                                     Risk of Death, by Day,                                             ...
Developing an Indicator to Measure Intrapartum Stillbirth and Immediate Neonatal Death•    GAPPS and MHTF sponsored meetin...
Practical Tools for Immediate and Near-term Impact•Scale up and improved quality of evidence-basedinterventions and childb...
Preventing Preterm Birth (PPB) Initiative  • GAPPS stewarding $20 million Gates Foundation    grant  • Advances research i...
The GAPPS Repository•   Collection of vital resources– Maternal data linked to tissue specimens•   Fosters pioneering rese...
Prevention of Prematurity and Stillbirth_Litch_10.11.12
Prevention of Prematurity and Stillbirth_Litch_10.11.12
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  • Maternal, fetal, newborn and child health are all linked. Prematurity and stillbirth interventions, many of which are directed toward the mother, will help improve all of these health outcomes. (click) These connected outcomes require a new, interdisciplinary approach.
  • *Note: Preterm birth may also be a major risk factor for other neonatal deaths.
  • The point of this slide - We’ve made great strides in improved management in NICU care in industrialized countries --- but basic services for late preterm deliveries would address the majority of preterm-related deaths
  • Don’t read list - just a way to underscore the multiple causes, and need for discovery of multiple solutions
  • Point of slide – preterm deaths occur at or soon after delivery Causes are complications of pregnancy and delivery - interventions need to be part of EmONC This slide could go before or after next slides on causes of death
  • Transcript of "Prevention of Prematurity and Stillbirth_Litch_10.11.12"

    1. 1. Prevention of Prematurity andStillbirth - Epidemiology, Evidence,and ResearchJames A. Litch, MD, DTMHDirector, Perinatal Interventions ProgramGlobal Alliance for Prevention of Prematurity andStillbirth (GAPPS)Clinical Assistant Professor,Department of Global HealthDepartment of Epidemiologyjlitch@yahoo.comjames.litch@seattlechildrens.org
    2. 2. Outline• Millennium Development Goals (MDGs) progress• Definitions• Epidemiology• What we know - Evidence review for interventions• What we don’t know - Research activities• Note - All numbers reported in this presentation are estimates impeded by a variety of assumptions and classification/reporting systems
    3. 3. Millennium Development Goals (MDGs)Global <5 child mortality rate hasdeclined by a third, from 89 deathsper 1,000 live births in 1990 to 60in 2009.All regions, except sub-SaharanAfrica, Southern Asia andOceania, have seen reductions of atleast 50 per cent.Number of deaths in childrenunder five worldwide declinedfrom 12.4 million in 1990 to8.1 million in 2009. Nearly 12,000 fewer children dying each day.
    4. 4. Millennium Development Goals (MDGs)In developing regions, maternalmortality ratio dropped by 34%between 1990 and 2008, from 440maternal deaths per 100,000 livebirths to 290 maternal deaths. Despite proven interventions thatcould prevent disability or deathduring pregnancy and childbirth,maternal mortality remains a majorburden.
    5. 5. ConnectedMNCH OutcomesConnected MNCH OutcomesRequire a New, Interdisciplinary ApproachRequire an Interdisciplinary Approach MaternalPreterm birth and stillbirth are Maternalinextricably linked with maternal,newborn and child health. Prematurity & Child Prematurity & Stillbirth Fetal ChildInterventions aimed at reducing Stillbirth Fetalpreterm births and stillbirths willaccelerate efforts towardachieving MDGs 4 and 5. Newborn Newborn
    6. 6. Definitions
    7. 7. Born Too Soon Report What is preterm birth? erm pret te era m od ks and wee ate <37 L to 32Definition of preterm birth: 84 %Babies born alive before 37 Very pretermcompleted weeks of 28 to <32 weeks 10%pregnancy Ex < 2 trem 5% 8 w ely ee pre ks ter mSource: Chap 5, Born Too Soon
    8. 8. What is stillbirth? • Classification for most LMIC is a birthweight of at least 1000 g or a gestational age of at least 28 weeks (third trimester stillbirth) – Essential for international comparability, poorly applied – New stillbirth estimates for 193 countries published in Lancet Series use this definition – WHO definition — a "fetal death late in pregnancy" and allows each country to define the gestational age at which a fetal death is considered a stillbirth for reporting purposes. Some countries define stillbirth as early as 16 weeks of gestation, whereas others use a threshold as late as 28 weeks (1000 g).If high In some high-income countriesused for all countries then the global total • income country stillbirth definitions were other definitions are used would be much higher – In UK stillbirths are counted from 24 weeksSource: Lawn JE, Blencowe H, Pattinson R, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How to – Ineg for USA with WHO definition 13,070, USA definition 27,500make the data count? Lancet 2011; published online April 14. DOI:10.1016/S0140-6736(10)62187-3. USA, Australia and New Zealand from 20 weeks
    9. 9. Epidemiology
    10. 10. Major Causes of Under-5 Deaths Globally Cause of Mortality Annual <5 Deaths Stillbirths 3.2 million Respiratory infections 2 million Diarrheal diseases 1.6 million Malaria 1.1 million Preterm births 1 million Childhood-cluster diseases 1 million HIV/AIDS 340,000 Tuberculosis 40,000 Sources: Jamison, Sonbol, Jamison et al. 2006; Lawn, Wilczynska-Ketende et al. 2006; Stanton, Lawn et al. 2006 Not counted
    11. 11. Changes inCauses ofNewborn Deaths
    12. 12. Born Too Soon ReportFirst ever national estimates of preterm birth for 192countries – where are the highest rates? 11 countries with preterm birth rates over 15% 1.Malawi 2.Congo 3.Comoros 4.Zimbabwe 5.E. Guinea 6.Mozambique 7.Gabon 8.Pakistan 9.Indonesia 10.Mauritania 11.Botswana Of the 11 countries with the highest rates, 9 are in AfricaNote: rates by country are available on the accompanying wall chart. Not applicable=non WHO Members StateSource: Blencowe et al National, regional and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis andimplications
    13. 13. Born Too Soon Report Preterm births – where are the biggest numbers? 10 countries account for 60% of the world’s preterm births 1.India 2.China 3.Nigeria 4.Pakistan 5.Indonesia 6.United States of America 7.Bangladesh 8.Philippines 9.Dem Rep Congo 10.Brazil Truly a global problem, affecting all countries60% are in South Asia and sub-Saharan Africa but with less care Note: rates by country are available on the accompanying wall chart. Not applicable=non WHO Members State Source: Blencowe et al National, regional and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications
    14. 14. Preterm Births by Gestational Age and Region for2010 • 75% of preterm deaths are in Sub- Saharan Africa and Southern Asia • 80% of 32-37 week preterm babies can survive with essential care • Level of care determined by gestational age
    15. 15. Causes of Death Due to Preterm BirthUnderlying Pathology Cause of DeathLung immaturity Hypoxia Acute respiratory distress syndrome (ARDS)Inability to tolerate labor Birth asphyxiaPoor temperature regulation HypothermiaInfection Sepsis PneumoniaPoor feeding Hypoglycemia Dehydration Pour weight gain
    16. 16. Challenges for Preterm Prevention: MultipleSocial, Biological, and Clinical Risk Factors• Chorioamnionitis • Poor nutrition• Bacterial vaginosis • Poor pregnancy weight gain• Periodontal disease • Maternal age• Maternal morbidity • Marital status• Incompetent cervix • Poverty• Low pre-pregnancy weight • Black race• Poor weight gain • Tobacco use• Twins, triplets • Substance use• Congenital malformations • Stress• Genetics • Physical exertion• Prior preterm birth
    17. 17. Country variation in stillbirth rates 10 countries account for 66% of the Stillbirth rates Stillbirth rates world’s stillbirths – (deaths per 1000 (deaths per 1000 and 66% of neonatal livebirths) livebirths) deaths and 60% of maternal deaths Lowest countries Lowest countries   ••Finland Finland (2)(2) 1. India ••Singapore (2) Singapore (2) 2. Pakistan 3. Nigeria Highest countries Highest countries 4. China 192. Nigeria (42) 192. Nigeria (42) 5. Bangladesh 193. Pakistan (47) 193. Pakistan (47) 6. Dem Rep Congo 7. Ethiopia 8. Indonesia 9. Tanzania 10. AfghanistanSource: The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How to make the data count? Lancet 2011; publishedonline April 14. DOI:10.1016/S0140-6736(10)62187-3. 2.6 million stillbirths 98% occur in low-income and middle-income countries
    18. 18. Stillbirths during labor – 1.2 million a yearSource: The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How to make the data count? Lancet 2011; publishedonline April 14. DOI:10.1016/S0140-6736(10)62187-3. Approximately of 40% of stillbirths are during labor
    19. 19. Causes of stillbirths Major causes: 1. Childbirth complications 2. Maternal infections in pregnancy (eg syphilis, malaria) 3. Maternal conditions, especially hypertension and diabetes 4. Fetal growth restriction 5. Congenital abnormalities These overlap with the causes of maternal and neonatal deathsSource: Lawn JE, Blencowe H, Pattinson R, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How tomake the data count? Lancet 2011; published online April 14. DOI:10.1016/S0140-6736(10)62187-3.
    20. 20. What we do know –Evidence for Interventions
    21. 21. 2010 Global Report on Preterm Birth & Stillbirth• Identified evidence-based interventions to preventpreterm birth and stillbirth• About 2,000 studies on preterm birth, stillbirth orrelated interventions were evaluated.• Out of 82 existing interventions, 49 were selectedfor in-depth reviews.• Selection was based on the presence of areasonable amount of evidence and relevance tolow- and middle-income countries.• Commissioned by Gates Foundation• Available at www.gapps.org
    22. 22. Summary of assessments for INTRAPARTUM preterm birth andstillbirth interventions (based on GRADE system)
    23. 23. Quality evidence and strong recommendation for LMICs to reduce the burden of preterm birthPrevention of preterm birth Premature baby care • Essential and extra newborn care (thermal care, feeding support,• Preconception care package Management of early breastfeeding, and vitamin K especially family planning preterm labor at delivery• Smoking cessation and •Prophylactic • Neonatal resuscitation employment safeguards of corticosteroids pregnant women (PG to prevent • Prolonged Skin-to-Skin Care recurrent preterm birth) •Antibiotics for • Management of premature babies pPROM• Antenatal care package with complications especially •Tocolytics to slow respiratory distress syndrome,• Effective childbirth care down labor infections and jaundice • Progressing towards neonatal intensive care Reduction of preterm Mortality reduction among birth babies born preterm Priority interventions for preterm baby care team due to unique capability of driving significant preterm mortality reduction in a cost-effective manner
    24. 24. Estimated Lives Saved of Premature Babies in Settingswith Universal Coverage of Basic Interventions (withoutNICU)520,000 lives (55%) saved of premature babies could be prevented if adequate management of preterm labor and birth. 760,000 lives (80%) saved if family planning included in model. 25
    25. 25. Born Too Soon ReportQuality evidence and strong recommendation for LMICs toreduce the burden of stillbirthPrevention of antepartum Prevention of intrapartumstillbirth stillbirth• Preconception care package Management of especially family planning intrapartum •Effective childbirth care• Antenatal care package/BPP complications• Periconceptual folic acid and •Neonatal resuscitation maternal nutrition •Management of •Progressing towards• Malaria in pregnancy (IPTp/ITN) prolonged labor comprehensive Emergency• Syphilis screening and treatment •Magnesium sulfate Obstetric Care• Diabetes screening and •Antibiotics management •Active management• Smoking cessation and fetal of third stage growth restriction management •Induction of labor at or beyond 41 completed weeks Reduction of antepartum Reduction of intrapartum stillbirth stillbirth
    26. 26. Modeling reduction in stillbirth 10 evidence-based interventions Interventions considered in the model 99% coverage Stillbirths Reduction 1 Periconceptual folic acid fortification Basic 27,000 1% 2 Malaria in pregnancy - ITNs & IPTp antenatal care 35,000 1% 3 Syphilis screening and treatment 136,000 5% 4 Hypertensive diseases in pregnancy and management Advanced 57000 2% 5 Diabetes screening and management antenatal care 24,000 1% 6 Fetal growth restriction management 107,000 4% 7 Induction of labor at or beyond 41 completed weeks 52,000 2% 8,9,10 Obstetric Care (3 levels of care) Childbirth care 696,000 28% Total Stillbirths Averted 1,134,000 45% 1.1 million stillbirths (45%) could be prevented. 1.6 million (70%) if family planning included in model.Source: Pattinson R et al. Stillbirths: how (30%) could deliver for mothers andby obstetric care alone. 0.7 million can health systems be prevented babies? Lancet 2011.
    27. 27. What we know about what works?
    28. 28. Born Too Soon Report Potential for lives saved through steroid injections for women in preterm labor Respiratory complications due to lung immaturity (RDS) are the commonest cause of death in preterm babies. Single course of antenatal steroids to women in preterm labour: •31% Mortality reduction (RR 0.69, 95% CI 0.58 to 0.81) for babies in settings where ventilation (+/-surfactant is standard of care (Cochrane review)) •53% reduction in mortality in 4 studies in middle income countries (RR 0.47, 95% CI 0.35 to 0.64) Dexamethasone is low cost (<$1) and available in many settings but low coverage in low and middle income settings One of the 13 priority medicines listed by UN Commodities Commission Could save about 400,000 babies each year if reached 95% of women in preterm labor (LiST analysis)Source: Chap 6 , Born too soon,
    29. 29. Born Too Soon ReportPotential for lives saved through continuous skin-to-skin careBaby is tied skin to skin with mother 24 hours a dayfor days/weeks providing•thermal care,•increased breastfeeding, better weight gain•reduced infections and links to additional supportive care, ifneeded, and earlier dischargeMortality reduction 51% for babies < 2000 gm, infacilities, clinically stable and started within one weekcompared to incubator careEffective entry point for care of preterm babies Could save about 450,000 babies each year if reached 95% of preterm babies (LiST analysis)Chap 5 and 5, Born too Soon>Impact data from Lawn et al ‘Kangaroo mother care’ to prevent neonatal deaths due to preterm birth complications. Int J Epid: 2010,Conde Aguedelo Cochrane review 2011
    30. 30. What We Want to Know -current research efforts
    31. 31. Missed delivery opportunities to reach pretermbabies with essential interventions Information Gap Availability Gap Development Gap
    32. 32. Thank youGlobal Alliance for the Prevention ofPrematurity and Stillbirth (GAPPS) leadsa collaborative, global effort to increaseawareness and accelerate innovativeresearch and development to makeevery birth a healthy birth. jlitch@yahoo.com james.litch@seattlechildrens.org 33
    33. 33. Highly cost effective • Childbirth care cost analysis • Cost per maternal death prevented is US$54,350 • Counting newborns and stillbirths this becomes $3,920 per death prevented • Total additional running cost of $10.9 billion for the 68 priority countries per year for full coverage of care with • 10 interventions for women, newborns and stillbirths • plus 5 maternal and newborn specific interventions US $2.32 per year per person in the 68 priority countries Affordable especially given results of 2.7 million lives savedSource: Pattinson R, Kerber K, Buchmannmaternal health should count Stillbirths:full effect Investment in E, et al, for The Lancet’s Stillbirths Series steering committee. the how can health systemsdeliver for mothers and babies? Lancet 2011; published online April 14. DOI:10.1016/S0140-6736(10)62306-9.
    34. 34. 10 Risk of Death, by Day, During the First Month of LifeDaily risk of death (per 1,000 survivors) 8 6 4 2 0 0 10 20 30 Day of life Lawn JE, et al, Lancet 2005;365(9462):891-900
    35. 35. Developing an Indicator to Measure Intrapartum Stillbirth and Immediate Neonatal Death• GAPPS and MHTF sponsored meeting to:• Re-evaluate the Intrapartum Stillbirth and Early Neonatal Death indicator described in “Monitoring emergency obstetric care: a handbook” • Establish a protocol for a prospective multi-country pilot study • Results:Working group developed a standardized protocolPilot study performed by Global Health NetworkIntrapartum mortality, early neonatal mortality and peripartum mortality indicatorsare all feasible with provision of fetal heart monitor assessment at admission tolabor ward New indicator allows collection of robust data to improve intervention trials
    36. 36. Practical Tools for Immediate and Near-term Impact•Scale up and improved quality of evidence-basedinterventions and childbirth decision tools•Accelerate new interventions coming down the pipeline•Shift awareness and attitudes of families and HCWs
    37. 37. Preventing Preterm Birth (PPB) Initiative • GAPPS stewarding $20 million Gates Foundation grant • Advances research into causes and mechanisms of preterm birth • First of the Family Health Grand Challenges in Global Health • Received applications from 320 researchers in 50 countries
    38. 38. The GAPPS Repository• Collection of vital resources– Maternal data linked to tissue specimens• Fosters pioneering research– Leads to diagnostics, prevention, therapeutics• Expanding, becoming global model– Launched with Washington hospitals: UW, Swedish, Yakima Valley Memorial– Designed to be self-sustaining 40
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