preterm birth interventions_james litch_10.16.13
TRANSCRIPT
Prevention of Preterm Birth and Complications: Evidence for Interventions and Opportunities for Action
James A. Litch, MD, DTMHDirector, Perinatal Interventions ProgramGlobal Alliance for Prevention of Prematurity and Stillbirth (GAPPS)
Clinical Assistant ProfessorDepartment of Global HealthDepartment of EpidemiologyUniversity of Washington
Outline
• Definitions and numbers• Strategic approach• Interventions to manage preterm birth• Interventions for care the preterm
newborn• Interventions to prevent preterm birth• Ready for Implementation?
Definitions and Numbers
Definition of preterm birth: Babies born alive before 37 completed weeks of pregnancy
What is preterm birth?
Late and moderate
preterm
32 to <37 weeks
84%
Very preterm28 to <32 weeks10%
Extremely preterm
< 28 weeks
5%
Source: Chap 5, Born Too Soon
Born Too Soon Report
Annual births by gestation age
Source: Chap 5, Born Too Soon
Born Too Soon Report
Source: Analysis using data from Blencowe et al., 2012; Cousens et al., 2011; Liu et
al., 2012
Strategic Approach
Connected MNCH OutcomesRequire a New, Interdisciplinary Approach
Maternal
Fetal
Newborn
Child
Prematurity &
Stillbirth
Connected MNCH OutcomesRequires an Interdisciplinary Approach
Maternal
ReproductiveHealth
Newborn
Child
Prematurity &
Stillbirth
Preterm birth and stillbirth are
inextricably linked with maternal,
newborn, child and RH health.
Interventions aimed at reducing
preterm births and stillbirths will
accelerate efforts toward
achieving MDGs 4 and 5.
Three-phase Approach to Preterm Birth
Image from Healthy Newborn Network Technical Guidance for Program Implementationhttp://www.healthynewbornnetwork.org/resource/technical-guidance-program-implementation
Preterm Birth as a direct cause of neonatal deaths – change between 2000 to 2010
Causes of Death Due to Preterm Birth
Underlying Pathology Cause of DeathLung immaturity Hypoxia
Acute respiratory distress syndrome (ARDS)
Inability to tolerate labor Birth asphyxia
Poor temperature regulation Hypothermia
Infection SepsisPneumonia
Poor feeding HypoglycemiaDehydrationPour weight gain
Additional risks specific to preterm newborns
• Hypoglycemia/dehydration/under-nutrition from feeding difficulties - coordinated suck and
swallow process only starts at 34 weeks
• Thermal instability - surface area to mass and metabolic issues
• Severe infections more common, and higher risk of dying infection
• Respiratory Distress Syndrome due to lung immaturity and lack of surfactant
• Jaundice - immature liver cannot easily metabolize bilirubin, and brain is at higher risk since
their blood-brain barrier is less well developed.
• Brain injury is most commonly intraventricular hemorrhage, occurring in the first few days after
birth in about 1 in 5 babies <2,000 g.
• Necrotizing enterocolitis affecting the intestinal wall of very premature babies. Formula feeding
increases risk tenfold compared to BF milk alone (Schanler, 2001).
• Retinopathy of prematurity if given too high levels of oxygen.
• Anemia of prematurity from immature bone marrow.
Interventions and Evidence
Essential Newborn Care plus Extra Care for Preterm Babies
Evidenced-based Interventions to Improve Preterm Survival
• ENC – thermal care, hygeine/handwashing, immediate breast feeding and resuscitation
• Antenatal corticosteroids• Antibiotics for preterm prelabor rupture of
the membranes (pPROM) • Delayed cord clamping • Chlorhexidine to chord• Kangaroo Mother Care (prolonged skin to
skin contact)• Surfactant therapy• Optimal feeding
Evidenced-based Interventions to Prevent Preterm Birth
• Birth spacing• Family planning• Treatment of infectious diseases (STI,
malaria, HIV)• Substance abuse / smoking cessation• Domestic violence
What works?
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)
Could save about 400,000 babies each year if reached 95% of women in preterm labor (LiST analysis)
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
Born Too Soon Report
Source: Chap 6 , Born too soon,
ACS: Clinical Guidelines
• WHO recommended treatment– Single dose for pregnant women who are:
• between 26 and 35 weeks gestational age, and• At risk of preterm delivery within 7 days
– Dexamethasone 6 mg IM 4 doses 12 hours apart*
– Betamethasone 12 mg IM, 2 doses 24 hours apart
• Insufficient evidence to justify multiple courses or a single rescue course of ANC at this time
• Partial or incomplete regimen may provide some benefit• Major barrier to implementation is identifying women at risk
or preterm labor in time to administer drug
Hofmeyer GJ. Antenatal corticosteroids for women at risk of preterm birth: RHL commentary. The WHO Reproductive Health Library; Geneva, WHO.Bonanno C, Wapner RJ. Antenatal Corticosteroids an the management of preterm birth: are we back where we started? 2012 Obstet Gynecol Clin N Am; 39:47-3-62.
Potential for lives saved through antibiotics for premature prelabor rupture of the membranes (pPROM)
- In high-income countries, it is standard practice to give antibiotics to women with pre-term, pre-labour rupture of membranes (pPROM) to delay birth and reduce the risk of infection.
- In LMICs use of antibiotic therapy for pPROM is not common- Reviewed 18 RCTs (most from HIC) that provide strong evidence
that antibiotics for pPROM:- Reduced risk of RDS [risk ratio (RR) = 0.88; confidence interval (CI)
0.80, 0.97], - Reduced risk of early onset postnatal infection (RR = 0.61; CI 0.48,
0.77). - Reduction in neonatal mortality (RR = 0.90; CI 0.72, 1.12).
- In LMICs where access to other interventions (antenatal steroids, surfactant therapy, ventilation, antibiotic therapy) may be low, antibiotics for pPROM could prevent 4% of neonatal deaths due to complications of prematurity and 8% of those due to infection.
Could save about 12% of PT babies each year if reached 95% of women in preterm labor (LiST
analysis)
Born Too Soon Report
Cousens S, et al. Antibiotics for preterm pre-labor rupture of membranes. International Journal of Epidemiology 2010;39:i134–i143.
Antibiotics for premature prelabor rupture of the membranes (PROM)
Lack of data from low-income countries, where newborns have less access to appropriate PT care.
In the absence advance PT interventions, the use of antibiotics for pPROM will certainly prevent neonatal deaths by preventing RDS.
Similarly, in settings with poor access to antibiotic therapy for neonatal infections, the prevention of sepsis cases through the use of antibiotics for pPROM will certainly prevent infection deaths.
Cousens S, et al. Antibiotics for preterm pre-labor rupture of membranes. International Journal of Epidemiology 2010;39:i134–i143.
Delayed chord clamping
Wait 2-3 minutes, or until chord stops pulsating, while keeping baby below level of placenta
There are different potential comparative effects of early rather than delayed cord clamping for term and preterm infants.
In term infant, increasing placental transfusion by delaying cord clamping may increase respiratory morbidity after birth (Yao 1974).
What about for PTB less than 37 weeks?
Born Too Soon: The Global Action Report on Preterm Birth. World Health Organization. Geneva, 2012Roberts d, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Reviews 2006. 3.
Potential for decrease morbidity and transfusions through delayed chord clamping for PTB < 37 weeks
Fifteen studies (738 infants) were eligible for inclusion. Participants were between 24 and 36 weeks’ gestation at birth. The maximum delay in cord clamping was 180 seconds. Delaying cord clamping, compared to immediate clamping, was associated with:
- Fewer infants requiring transfusions for anaemia (seven trials, 392 infants; risk ratio (RR) 0.61, 95% confidence interval (CI) 0.46 to 0.81)
- Less intraventricular haemorrhage (ultrasound diagnosis all grades) 10 trials, 539 infants (RR 0.59, 95% CI 0.41 to 0.85)
- Lower risk for necrotising enterocolitis (five trials, 241 infants, RR 0.62, 95% CI 0.43 to 0.90)
For primary outcomes of infant death, severe intraventricular hemorrhage and periventricular leukomalacia there were no clear differences identified between groups
Decreased complications and reduced transfusionneeds if reached 95% of preterm newborns
Born Too Soon Report
Source: Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and 15 infant outcomes (2012 Cochrane Review)
Delayed chord clamping for PTB < 37 weeks
• Developing countries, with limited resources and a high risk of transmitting infection through blood transfusion
• Potential value of a reduced need for blood transfusion.
• In more developed countries, 60% to 80% of preterm infants less than 32 completed weeks’ gestation (Brune 2002; Ringer 1998) require transfusion
Born Too Soon: The Global Action Report on Preterm Birth. World Health Organization. Geneva, 2012Roberts d, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Reviews 2006. 3.
Resuscitation for preterm baby
- Premature births have higher risk of hypoxic brain injury and retinopathy from oxygen administration.
- Some 10% of newborns require assistance to begin breathing, more for preterm babies
- ¾ of these require only basic resuscitation with bag and mask or tube and mask to initiate breathing
- Assisted ventilation with room air is equivalent to using oxygen (Saugstad et al, 2006)
- Premature babies at great risk for RDS and may require ventilation support with CPAP
Emollient ointment for preterm newborn
- Topical application of emollient ointment (sunflower oil or Aquaphor/Petrolatum 41%)
- Reduces water loss, dermatitis and risk of sepsis (Soll and Edwards, 2000)
- Limited hospital-based trials in Egypt and Bangladesh (reduced mortality)
- High potential and has application in facilities and homes
Chlorhexidine topical application
- Topical application of 7.1% chlorhexidine digluconate solution/gel to chord before 24 hours of birth (continue up to 7 days)
- Reduces chord stump infection and risk of sepsis (Tielsch et al, 2007, Scoofi et al, 2012, Arifeen et al, 2012)
- Community trials in Asia and Africa - Greater reduction of mortality among preterm
newborns (Arifeen et al 2012)
Clean birth practices for preterm newborn
- Consistent hand washing and maintaining a clean environment
- Premature births have higher risk of sepsis.
- Included in: - Continuous skin to skin care package (KMC)- Clean birth kits
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•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
Chap 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
Could save about 450,000 babies each year if reached 95% of preterm babies (LiST analysis)
Born Too Soon Report
Feeding Support
- Early initiation of breast feeding within one hour after birth reduces (Edmond et al, 2006)
- Premature newborns benefit nutritionally, immunologically and developmentally (Callen and Pinelli, 2005)
- Formula feeding increases risk of necrotizing enterocolitis and improved neurodevelopmental outcome (Edmond et al, 2007; Hurst, 2007)
- Extra feeding support with a cup, spoon or other device (especially <34 weeks)
- Support mother expressing milk or provide donor milk- Milk banking is option in some areas of Africa
Likely to work – but lacking evidence for preterm lives saved
- Birth preparedness - Danger signs awareness- Monitoring of labor- Transportation / referral arrangements- Mother/Baby friendly care (patient centered respectful care)- Postnatal care vouchers
Prevention of preterm birth Care before and between pregnancy
Implement:
• Family planning strategies, including birth spacing and provision of adolescent-friendly services
• Prevention and management of STIs and NCDs
• Education and interventions for domestic violence
• Promotion of healthy nutrition and addressing life-style risks like smoking and substance abuse
Source: Born Too Soon
Implementation
Where 15 million preterm babies receive care
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Estimated Lives Saved of Premature Babies in Settings with Universal Coverage of Basic Interventions (without NICU)
520,000 lives (55%) of premature babies could be saved if adequate management of preterm labor and birth.
760,000 lives (80%) saved if family planning included in model.
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Thank you
Global Alliance to Prevent 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.
Important Resources
www.biomedcentral.com/bmcpregnancychildbirth/supplements/
www.who.int/pmnch/media/news/2012/preterm_birth_report/en/index.html
Born Too soon: The Global Action Report on Preterm Birth
Essential Interventions, Commodities and Guidelines for Reproductive, Maternal, Newborn and Child Health
Global report on preterm birth & stillbirth: the foundation for innovative solutions and improved outcomes
www.who.int/pmnch/topics/part_publications/201112_essential_interventions/en/index.html
Interventions for preterm birth and stillbirthalong the continuum of care
PRE-PREGNANCY
CHILDHOODPOSTNATAL/ NEWBORN
BIRTHPREGNANCY
•Family planning/birth spacing•Prevent & treat sexually transmitted infections•Nutrition
•Prevent & treat sexually transmitted infections•Nutrition
•Antenatal steroids•Antibiotics for pPROM•Delayed chord cutting•Identify preterm babies
•Essential & Extra care•Chlorhexidine•Kangaroo Mother Care•Management of sick newborns•Neonatal resuscitation•Appropriate oxygen use•Ventilation support•Postnatal followup
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