1. Prevention of Prematurity and
Stillbirth - Epidemiology, Evidence,
and Research
James A. Litch, MD, DTMH
Director, Perinatal Interventions Program
Global Alliance for Prevention of Prematurity and
Stillbirth (GAPPS)
Clinical Assistant Professor,
Department of Global Health
Department of Epidemiology
jlitch@yahoo.com
james.litch@seattlechildrens.org

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. Millennium
Development
Goals (MDGs)
Global <5 child mortality rate has
declined by a third, from 89 deaths
per 1,000 live births in 1990 to 60
in 2009.
All regions, except sub-Saharan
Africa, Southern Asia and
Oceania, have seen reductions of at
least 50 per cent.
Number of deaths in children
under five worldwide declined
from 12.4 million in 1990 to
8.1 million in 2009.
Nearly 12,000 fewer children dying each day.

4. Millennium
Development
Goals (MDGs)
In developing regions, maternal
mortality ratio dropped by 34%
between 1990 and 2008, from 440
maternal deaths per 100,000 live
births to 290 maternal deaths.
Despite proven interventions that
could prevent disability or death
during pregnancy and childbirth,
maternal mortality remains a major
burden.

5. ConnectedMNCH Outcomes
Connected MNCH Outcomes
Require a New, Interdisciplinary Approach
Require an Interdisciplinary Approach
Maternal
Preterm birth and stillbirth are Maternal
inextricably linked with maternal,
newborn and child health.
Prematurity &
Child
Prematurity & Stillbirth Fetal
Child
Interventions aimed at reducing Stillbirth Fetal
preterm births and stillbirths will
accelerate efforts toward
achieving MDGs 4 and 5.
Newborn
Newborn

6. Definitions

7. Born Too Soon Report
What is preterm birth?
erm
pret
te
era
m od ks
and wee
ate <37
L to
32
Definition of preterm birth: 84
%
Babies born alive before 37 Very preterm
completed weeks of 28 to <32 weeks
10%
pregnancy
Ex
< 2 trem
5% 8 w ely
ee pre
ks ter
m
Source: Chap 5, Born Too Soon

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 weeks
Source: 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 27,500
make 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. Epidemiology

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. Changes in
Causes of
Newborn Deaths

12. Born Too Soon Report
First ever national estimates of preterm birth for 192
countries – 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 Africa
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

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 countries
60% 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. Preterm Births by Gestational Age and Region for
2010
• 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. Causes of Death Due to Preterm Birth
Underlying Pathology Cause of Death
Lung immaturity Hypoxia
Acute respiratory distress syndrome (ARDS)
Inability to tolerate labor Birth asphyxia
Poor temperature regulation Hypothermia
Infection Sepsis
Pneumonia
Poor feeding Hypoglycemia
Dehydration
Pour weight gain

16. Challenges for Preterm Prevention: Multiple
Social, 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. 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. Afghanistan
Source: The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How to make the data count? Lancet 2011; published
online April 14. DOI:10.1016/S0140-6736(10)62187-3.
2.6 million stillbirths
98% occur in low-income and middle-income countries

18. Stillbirths during labor – 1.2 million a year
Source: The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How to make the data count? Lancet 2011; published
online April 14. DOI:10.1016/S0140-6736(10)62187-3.
Approximately of 40% of stillbirths are during labor

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 deaths
Source: Lawn JE, Blencowe H, Pattinson R, et al, for The Lancet’s Stillbirths Series steering committee. Stillbirths: Where? When? Why? How to
make the data count? Lancet 2011; published online April 14. DOI:10.1016/S0140-6736(10)62187-3.

20. What we do know –
Evidence for Interventions

21. 2010 Global Report on Preterm Birth & Stillbirth
• Identified evidence-based interventions to prevent
preterm birth and stillbirth
• About 2,000 studies on preterm birth, stillbirth or
related interventions were evaluated.
• Out of 82 existing interventions, 49 were selected
for in-depth reviews
.
• Selection was based on the presence of a
reasonable amount of evidence and relevance to
low- and middle-income countries.
• Commissioned by Gates Foundation
• Available at www.gapps.org

23. Summary of assessments for INTRAPARTUM preterm birth and
stillbirth interventions (based on GRADE system)

24. Quality evidence and strong recommendation for LMICs to
reduce the burden of preterm birth
Prevention 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

25. Estimated Lives Saved of Premature Babies in Settings
with Universal Coverage of Basic Interventions (without
NICU)
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

26. Born Too Soon Report
Quality evidence and strong recommendation for LMICs to
reduce the burden of stillbirth
Prevention of antepartum Prevention of intrapartum
stillbirth 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

27. 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.

28. What we know about what works?

29. 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,

30. Born Too Soon Report
Potential for lives saved through continuous skin-to-skin care
Baby is tied skin to skin with mother 24 hours a day
for days/weeks providing
•thermal care,
•increased breastfeeding, better weight gain
•reduced infections and links to additional supportive care, if
needed, and earlier discharge
Mortality reduction 51% for babies < 2000 gm, in
facilities, clinically stable and started within one week
compared to incubator care
Effective 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

31. What We Want to Know -
current research efforts

32. Missed delivery opportunities to reach preterm
babies with essential interventions
Information Gap Availability Gap
Development Gap

33. Thank you
Global Alliance for the Prevention of
Prematurity and Stillbirth (GAPPS) leads
a collaborative, global effort to increase
awareness and accelerate innovative
research and development to make
every birth a healthy birth.
jlitch@yahoo.com
james.litch@seattlechildrens.org
33

35. 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 saved
Source: 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 systems
deliver for mothers and babies? Lancet 2011; published online April 14. DOI:10.1016/S0140-6736(10)62306-9.

36. 10
Risk of Death, by Day,
During the First Month of Life
Daily 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

37. 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 protocol
Pilot study performed by Global Health Network
Intrapartum mortality, early neonatal mortality and peripartum mortality indicators
are all feasible with provision of fetal heart monitor assessment at admission to
labor ward
New indicator allows collection of robust data
to improve intervention trials

38. Practical Tools for Immediate and Near-
term Impact
•Scale up and improved quality of evidence-based
interventions and childbirth decision tools
•Accelerate new interventions coming down the pipeline
•Shift awareness and attitudes of families and HCWs

39. 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

40. 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