Prevention and Care for Babies Born Too Soon

Global Newborn Health Conference Johannesburg, South Africa April 16, 2013

Cyril M. Engmann MD FAAP

Senior Program Officer, Neonatal Health Maternal, Newborn and Child Health Program Bill & Melinda Gates Foundation

EVERY PERSON, INCLUDING NEWBORNS DESERVES THE CHANCE TO LIVE A HEALTHY, PRODUCTIVE LIFE.
Outline Preterm burden Implementation & research horizons Purpose-driven, catalytic partnerships

2013 Bill & Melinda Gates Foundation

15 Million Preterm births a global problem

10 countries
account for 60% of the worlds preterm births
1. 2. 3. 4. 5. 6. India China Nigeria Pakistan Indonesia United States of America 7. Bangladesh 8. Philippines 9. Dem Rep Congo 10. Brazil

PRETERM BIRTH: BIRTH BEFORE 37 COMPLETED WEEKS OF GESTATION

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

Preterm birth also a major issue in highincome countries

United States among top ten countries in terms of number of preterm births
India

Preterm birth costs developed world ~$40B per year

IOM report from 2007 found that preterm birth cost the US $26.2B per year1

China
Nigeria Pakistan Indonesia USA Bangladesh Philippines Dem Rep Congo Brazil 774 1,172

3,519

748
676 517 424 349 341 279 0 1,000 2,000 3,000 4,000

Extrapolating to rest of developed world based on per-capita HC spend and PT birth rate suggests cost of ~$40B annually

2010 preterm births ('000)

Creates unique opportunity to leverage investments & learning from low- and middle- and high-income countries to improve preterm birth and newborn health
1. Includes costs of medical care services, early intervention services, special education services, and lost household and labor market productivity. Methods: total economic cost associated with 1 preterm baby estimated to be $51,600 in the US in 2005 (Behman et al). Estimate for other countries obtained by scaling each country's per capita health expenditure in 2005 to that of the US. Total economic cost saved for a given country is cost per PTB infant x projected number of preterm births averted . Total sum here for all 42 UN high human development index countries (in green). Source: World Bank statistics, Behrman et al. (2007) Institute of Medicine: Preterm Birth: Causes, Consequences, and Prevention, Born Too Soon; BCG analysis

1.1 million preterm deaths each year

> 125 deaths per hour = Commercial liner crashing every 3 hours

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Neonatal mortality is declining slower than child mortality and prematurity is the 2nd leading cause of under-5 deaths 2010 Childhood Mortality
Neonatal mortality is not dropping as fast as under-five mortality 40% Neonatal Period Preterm birth is the #2 cause of U5 death
Under 5 Mortality Neonatal Mortality

35%

Preterm

23%

Intrapartum

27%

Infection

15%

Other

Infection includes: sepsis, pneumonia, tetanus and diarrhea

Source: Lawn J E et al. Health Policy Plan. 2012;27:iii6-iii28; Liu L et al. Lancet. 2012; 79(9832):2151-61.

Long-term impact of preterm birth on survivors

Long-term outcomes Specific physical effects Visual impairment Hearing impairment Chronic lung disease of prematurity Long-term cardiovascular ill-health and non-communicable disease

Neuro-developmental/ behavioral effects

Mild: disorders of executive functioning Moderate to severe: global developmental delay Psychiatric/behavioral sequalae Impact on family Impact on health service Intergenerational

Family, economic and societal effects

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 Born Too Soon

The Global Action Report on Preterm Birth

Born Too Soon - a truly global report

First global estimates of preterm birth rate for 184 countries with WHO (Lancet, 2012) > 50 partner organizations including 45 authors from 11 countries including scientists, epidemiologists, clinicians, parents Linked to Every Woman Every Child, and forward by UN Secretary General Ban Ki-Moon

Professionals, policymakers and parents

Free at www.who.int/pmnch/media/news/2012/preterm_birth_report/en/index.html
2013 Bill & Melinda Gates Foundation |

Two groups formed to channel momentum from Born Too Soon into actionable steps
Research Group Care Group Purpose: Accelerate implementation of priority interventions Core Members: UNICEF, WHO, SNL, USAID, BMGF, CIFF, AAP/IPA, PMNCH Next steps: Efforts feeding into Global Newborn Actionwith a Plan to be launched later this year

Purpose: Develop a preterm research solution pathway

Core Conveners: NICHD GAPPS, MOD, BMGF, WHO @ Researchers Next steps: Convene a funders meeting in summer 2013 to coordinate global preterm funding efforts

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www.facebook.com/worldprematurityday

What: A global movement to accelerate access to simple, cost-effective solutions, and support families who have experienced preterm birth. Who: > 55 global partners and > 60 countries, all continents, media reach of 1.4 billion High income countries, e.g. Illumination Initiative for famous buildings

Malawi: high level event, commitment made Uganda: high level event with Minister of Health, commitment made for KMC and ACS scale up

India: Global KMC meeting in Ahmedabad, India, etc

Global twitter relay 28 million reached

#Borntoosoon #WorldPrematurityDay

Outline Preterm burden

Implementation & research horizons

Purpose-driven, catalytic partnerships

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Priority interventions -'tip of the spear' to drive maximal impact

Utilize high impact priority interventions to drive a wedge...

Infection case management Cervical pessary CPAP / novel surfactant Neonatal resuscitation

ANCS

KMC

...and to provide the platform for implementing future innovations

...for other critical interventions to be implemented in a package...

Kangaroo mother care

Skin-to-skin with mother 24 hours a day providing: Exclusive breastfeeding Supportive care for the mother infant dyad
Improved mortality (LMIC: RR 0.58, 95% CI 0.37-0.9 @ 40/41 or discharge) Reduced infections (LBW: 7.2% vs. 12.6% RR 0.57, CI: 0.4-0.8 @ 6/12) Improved infant growth (Weight: MD 3.9g/day; Length: MD 0.29cm/day; HC:
0.18cm/week)

Reduced hypothermia (RR 0.23, 95% CI 0.1-0.55) Mothers more likely to breastfeed @ 3/12 (RR 1.2, Earlier discharge (2.4 days on average) Increased maternal infant attachment (24 vs. 18)

95% CI 1.01-1.43)

Effective entry point for care of small babies

Could save an estimated 450,000 babies by 2015 if 95% of preterm babies are reached
Lawn et al Kangaroo mother care to prevent neonatal deaths due to preterm birth complications. Int J Epid: 2010, Conde-Agudelo A, Belizan JM, Diaz-Rossello, Cochrane Review: 2011

We are working to overcome barriers to wider use of Kangaroo Mother Care

Barrier
Factional and uncoordinated global community. ? Over-medicalization by the medical profession, creating the perception that KMC is so hard, babies are so fragile, KMC must be done just right, and are babies safe resulting in making KMC so complex Lack of cohesive national policies with quality control and M&E components Lack of integration - KMC often limited to referral centers Limited demand among families for postnatal services

Action
Conduct faction analysis, partner landscaping and apply a systems approach Catalyze coordinated thinking, communication and action among partners, and align around common goals Elaborate the fact base for KMC and identify points of alignment vs. points of contention

Integrate recordkeeping and reporting on KMC into routine monitoring and evaluation systems Countries self-selected to become champions Promote a KMC continuum of care culture and framework Promote early care-seeking through community engagement Understand social support needs of moms and families to practice KMC

Sources: MCHIP, Save the Children (2012). Tracking Implementation Progress for Kangaroo Mother Care.

Groundswell of newborn community asking questions of KMC and building momentum

WHO CHNRI Exercise, KMC was Top of the list for preterm birth questions Among top 10 newborn research priorities
Evaluate the effectiveness, safety and cost of community-based initiation of KMC to improve survival and health outcomes of clinically stable preterm and LBW babies
Evaluate strategies for scale up of facility-based initiation of KMC for preterm and LBW babies on their survival, health and long-term outcomes such as school-performance

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We are working to overcome contextual barriers to wider use of antenatal corticosteroids

Barrier
Lack of awareness, knowledge, guidelines & local regulations about who can administer drug; lack of and/or belief among healthcare providers

Action
Application to add to WHO Essential Medicines List Policy brief for use at country level Frequently asked questions to dispel myths Online portal for quick reference to key information In-country education and training

Lack of supply at the right place and right time

Identification of multiple, low cost (<$1/dose) generic suppliers Technical support to UN Commission country plans to specifically address supply constraints Community mobilization to identify danger signs in pregnancy and ensure transport to health facility Caregiver training on basic measurement of gestational age

Late presentation of mother

Sources: Althabe F et al, Reproductive Health 2012 ; Born Too Soon Care Group; Lawn JE, Segre J et al. Antenatal Corticosteroids for the reduction of deaths in preterm babies. UN Commission Report. March 2012

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We are working with research and funding partners to map out a preterm solution pathway to coordinate our efforts
Research group Care group

Discovery

Development
PTB biomarkers Fetal Fibronectin
Requires validation of high potential options and dev. of field ready Dx

Delivery

Predict preterm births

Understand etiopathogenesis of PTB & develop interventions to predict and prevent PTBs
Requires clearly defined research agenda and more traction from research and funding communities

Mainly used to rule out PTB, has low positive predictive value

Cervical length measurement

Requires dev of suitable methods for use in low resource settings

Social factors
e.g. stress

Assessment of prior PTB hx

Requires dev. of suitable methods for use in low resource settings

Progesterone
Requires tools to enable deployment & user friendly formulation

Prevent preterm births

Cervical pessary
Very promising but requires validation and tools to enable deployment

Care for the preterm baby

Community KMC
Being implemented in select locations but still requires more operational research before widespread uptake

Institutional KMC
Requires effort to drive uptake

Novel surfactant
Requires more user friendly & inexpensive formulation

CPAP
Requires adaptation for use in low resource settings

Antenatal Corticosteroids
Requires effort to drive uptake

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Preterm birth research horizons to fill the gaps of known interventions

Biomarkers, proteomics, pessaries, progesterone.

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First published RCT assessing use of cervical pessary in PTB showed efficacy on all end points
Women with cervical length 25mm randomized to pessary or control
726 women with cervix 25mm
341 opted out

Meaningful efficacy seen on all pregnancy and neonatal outcomes

Relative Risk
Pregnancy PTB < 28 wks PTB < 34 wks PTB < 37 wks 0.0 0.5 1.0 0.25 [0.09-0.73] 0.24 [0.13-0.43] 0.36 [0.27-0.49] 0.35 [0.17-0.72] 0.30 [0.18-0.50]

385 randomly assigned

BW < 1500 g
192 assigned to cervical pessary
2 lost to follow up

193 assigned to expectant mgt.

3 lost to follow up

BW < 2500 g Neonatal RDS Sepsis Rx Composite

0.22 [0.08-0.56] 0.25 [0.07-0.87] 0.17 [0.07-0.42]

190 included in intention-to-treat analysis

190 included in intention-to-treat analysis

While impressive, consensus is that more trials are needed to confirm RCT findings
Source: Goya et al. Lancet (2012): Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial, Data from Goya et al study converted into relative risk and 95% CI using online calculator from Centre for Evidence Based Medicine, Toronto which is accessible at http://ktclearinghouse.ca/cebm/practise/ca/calculators/statscalc BCG analysis

Cochrane meta-analysis by Dodd et al. showed benefit of progesterone1 in women with different PTB risk profiles

Relative Risk Short cervix2

0.0 0.2 0.4 0.6 0.8 1.0

[95% CI]

PTB < 34 wks Neonatal sepsis

RR 0.58 [0.38-0.87] RR 0.28 [0.08-0.97]

PTB history
PTB < 34 wks PTB < 37 wks BW < 2500 g RR 0.15 [0.04-0.64] RR 0.80 [0.70-0.92]

RR 0.64 [0.49-0.83]
RR 0.75 [0.57-0.97]

Multiple pregnancy
Risk of tocolysis

Threatened PT labor
PTB < 37 wks

RR 0.29 [0.12-0.69]

1. Cochrane review did not differentiate between subtypes of progesterone (natural progesterone vs. synthetic 17-alpha-hydroxyprogesterone caproate (17P)). 2. Short cervix definition varies, and Cochrane review included only cervical length < 15 mm Source Dodd et al. Cochrane Library (2012), Romero. Women's Health (2011), BCG analysis

The late preterm @ 32-36 weeks (85% of PTB) more prone to adverse effects than @ 40 weeks

Outline Preterm burden

Implementation & research horizons

Purpose-driven, catalytic partnerships

2013 Bill & Melinda Gates Foundation

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We cannot view newborn health in isolation. We must take a holistic, panoramic view involving catalytic partnerships
Partnerships can lead to better, faster, greater health outcomes within the context of healthy and productive families

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What Can You Do?

1. Policy: include newborn and preterm birth in policy
frameworks

2. Program: ANCS & KMC; measure, quality of care

3. Form purpose-driven partnerships: across RMNCH, nutrition, malaria, education

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The task is not impossible

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A single spider weaves a web and catches one fly,

Many spiders weave a web and catch an elephant.

-Ghanaian proverb

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Thank You

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