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...
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           ...
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 labour – 1.2 million a year                              Approximately of 40% of stillbirths are during...
Major Causes of stillbirths                1. Childbirth complications                2. Maternal infections in pregnancy ...
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  ...
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...
Thank youGlobal Alliance to Prevent Prematurityand Stillbirth (GAPPS) leads acollaborative, global effort to increaseaware...
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  • *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
  • Jim litch core meeting final handout upload

    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. 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
    6. 6. 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). • In some high-income countries other definitions are used – In UK stillbirths are counted from 24 weeks – In USA, Australia and New Zealand from 20 weeks If high income country stillbirth definitions were used for all countries then the global total would be much higher eg for USA with WHO definition 13,070, USA definition 27,500Source: 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.
    7. 7. 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 Not counted Sources: Jamison, Sonbol, Jamison et al. 2006; Lawn, Wilczynska-Ketende et al. 2006; Stanton, Lawn et al. 2006
    8. 8. Changes inCauses ofNewborn Deaths
    9. 9. 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
    10. 10. 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 countries 60% are in South Asia and sub-Saharan Africa but with less careNote: 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
    11. 11. 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
    12. 12. 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
    13. 13. 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
    14. 14. Country variation in stillbirth rates 10 countries Stillbirth rates Stillbirth rates account for 66% (deaths per 1000 (deaths per 1000 livebirths) of the world’s livebirths) stillbirths – Lowest Lowest and 66% of countries countries neonatal deaths 1.Finland 1.Finland (2) (2) and 60% of 2.Singapore (2) 2.Singapore (2) maternal deaths 1. India Highest Highest 2. Pakistan countries countries 3. Nigeria 192. Nigeria 192. Nigeria 4. China (42) (42) 5. Bangladesh 193. 193. Pakistan Pakistan 6. Dem Rep (47) (47) Congo 7. Ethiopia 8. Indonesia 9. Tanzania 10. AfghanistanSource: Lawn JE, Blencowe H, Pattinson R, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? Howto make the data count? Lancet 2011; published online April 14. DOI:10.1016/S0140-6736(10)62187-3. 2.6 (2.08 to 3.79) million stillbirths 98% occur in low-income and middle-income countries
    15. 15. Stillbirths during labour – 1.2 million a year Approximately of 40% of stillbirths are during laborSource: Lawn JE, Blencowe H, Pattinson R, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? Howto make the data count? Lancet 2011; published online April 14. DOI:10.1016/S0140-6736(10)62187-3.
    16. 16. Major Causes of stillbirths 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.
    17. 17. 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
    18. 18. Summary of assessments for INTRAPARTUM preterm birth andstillbirth interventions (based on GRADE system)
    19. 19. 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• Preconception care package support, early breastfeeding, Management of especially family planning and vitamin K at delivery preterm labor• Smoking cessation and • Neonatal resuscitation •Prophylactic employment safeguards of corticosteroids • Prolonged Skin-to-Skin Care pregnant women (PG to prevent recurrent preterm birth) •Antibiotics for • Management of premature pPROM babies with complications• Antenatal care package especially respiratory distress •Tocolytics to slow syndrome, infections and• Effective childbirth care down labor jaundice • Progressing towards comprehensive 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
    20. 20. 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. 21
    21. 21. Born Too Soon ReportQuality evidence and strong recommendation for LMICs toreduce the burden of stillbirthPrevention of antepartum Prevention of intrapartumstillbirth stillbirth Management of• Preconception care package intrapartum •Effective childbirth care especially family planning complications• Antenatal care package/BPP •Management of• Periconceptual folic acid and prolonged labor •Neonatal resuscitation maternal nutrition •Magnesium sulfate •Progressing towards• Malaria in pregnancy (IPTp/ITN) •Antibiotics comprehensive Emergency• Syphilis screening and treatment •Active management Obstetric Care• Diabetes screening and of third stage management •Induction of labor at• Smoking cessation and fetal or beyond 41 growth restriction management completed weeks Reduction of antepartum Reduction of intrapartum stillbirth stillbirth
    22. 22. Modeling reduction in stillbirth: 10 evidence-based interventions Interventions considered in the model 99% coverage Stillbirths Reduction 1 Periconceptual folic acid fortification Basic antenatal 27,000 1% 2 Malaria in pregnancy - ITNs & IPTp 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. 0.7 million (30%) could be prevented by obstetric care alone. But need higher coverage and quality of careSource: Pattinson R et al. Stillbirths: how can health systems deliver for mothers and babies? Lancet 2011.
    23. 23. 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,
    24. 24. 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
    25. 25. Thank youGlobal Alliance to Prevent Prematurityand Stillbirth (GAPPS) leads acollaborative, global effort to increaseawareness and accelerate innovativeresearch and development to makeevery birth a healthy birth. jlitch@yahoo.com james.litch@seattlechildrens.org

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