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Outcomes at 24 to 26 Weeks Outcomes at 24 to 26 Weeks GestationGestation

Thomas K. Shimotake, M.D.Thomas K. Shimotake, M.D.Assistant Professor of PediatricsAssistant Professor of Pediatrics

Associate Clinical Director for Neonatal ProgramsAssociate Clinical Director for Neonatal ProgramsWilliam H. Tooley Intensive Care Nursery William H. Tooley Intensive Care Nursery

University of California San FranciscoUniversity of California San Francisco

IntroductionIntroductionOver past two decades, survival of extremely Over past two decades, survival of extremely preterm infants (ELBW) <1000gm or <~27wk GA preterm infants (ELBW) <1000gm or <~27wk GA has gradually improved.has gradually improved.

Advances in:Advances in:•• OB careOB care•• Antenatal referral to major centersAntenatal referral to major centers•• Antenatal corticosteroid useAntenatal corticosteroid use•• Advances in respiratory support (eg, surf, vents)Advances in respiratory support (eg, surf, vents)•• Improved nutrition/TPNImproved nutrition/TPN•• Improved nursing careImproved nursing care•• Quality Improvement Initiatives (eg, iatrogenic infections)Quality Improvement Initiatives (eg, iatrogenic infections)

Survival vs. intact survivalSurvival vs. intact survival

What is the current GA at which at least half of the What is the current GA at which at least half of the infants survive?infants survive?

•• 1960s: 1960s: 3030--31 31 weeks GAweeks GA•• Currently:Currently: 2323--24 24 weeks GAweeks GA

But the pace of improvement in longBut the pace of improvement in long--term term neurodevelopmental outcomes has lagged.neurodevelopmental outcomes has lagged.

Concerns remain over longConcerns remain over long--term outcomes which term outcomes which may influence policy and guidelines for resuscitation.may influence policy and guidelines for resuscitation.

How to proceed?How to proceed?

Practice patterns at the threshold of viability are Practice patterns at the threshold of viability are influenced by many factors. influenced by many factors.

What should be considered?What should be considered?•• National/Worldwide data on mortality of ELBW?National/Worldwide data on mortality of ELBW?•• National/Worldwide data on longNational/Worldwide data on long--term outcomes?term outcomes?•• Population/InstitutionPopulation/Institution--specific data on mortality and specific data on mortality and

longlong--term outcomes?term outcomes?•• Parental wishes (Patient Autonomy)?Parental wishes (Patient Autonomy)?•• Physician judgment (Futility)?Physician judgment (Futility)?

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<23 weeks GA (below ~<400<23 weeks GA (below ~<400--500gm): 500gm): •• outcomes remain pooroutcomes remain poor•• Mortality > 90%Mortality > 90%•• Morbidity among survivors even worse.Morbidity among survivors even worse.

>26 weeks GA (above ~750gm):>26 weeks GA (above ~750gm):•• Outcomes are pretty goodOutcomes are pretty good

•• Mortality ≤ 30%Mortality ≤ 30%

What happens in between 23What happens in between 23--26 weeks? 26 weeks? •• “The Gray Zone”“The Gray Zone” Costeloe K, et. al., EPICure2, 2009

Robertson C, et al., Ped Neurol, 2009Singh J et. al.,, Pediatrics, 2007Vohr B, et. al., Vohr B, et. al., PediatricsPediatrics, 2000, 2000Hack M, et. al., Hack M, et. al., N Engl J MedN Engl J Med, 2000, 2000

Describing “survival limits”Describing “survival limits” Grey zone by birth weight or gestational age?Grey zone by birth weight or gestational age?500gm (~23wk GA) to 1000gm (~27wk GA) 500gm (~23wk GA) to 1000gm (~27wk GA)

Fenton, TR., A new growth chart for preterm babies: BMC Pediatrics, 2003

What is the data on outcomes of What is the data on outcomes of extremely low birth weight extremely low birth weight

infants? infants?

National/WorldwideNational/WorldwideMORTALITYMORTALITY

346 Vermont Oxford Network NICU’s worldwide346 Vermont Oxford Network NICU’s worldwide

n = 4172 infants born with BWt=400n = 4172 infants born with BWt=400--500gm 500gm

mean BWt: mean BWt: 457.8gm457.8gm

mean GA: mean GA: 23.3 23.3 ±±±±±±±±2.1 weeks2.1 weeks

52% 52% died in DR died in DR

63% of initial survivors died in NICU63% of initial survivors died in NICU

Overall survival to discharge: Overall survival to discharge: 17%17%

Survival to discharge of micropremies Survival to discharge of micropremies Vermont Oxford Network (1996Vermont Oxford Network (1996--2000)2000)

Lucey, JF, et. al., Vermont Oxford Network, Lucey, JF, et. al., Vermont Oxford Network, Pediatrics,Pediatrics, Jun 2004Jun 2004

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Lucey, JF, et. al., Vermont Oxford Network, Lucey, JF, et. al., Vermont Oxford Network, Pediatrics,Pediatrics, Jun 2004Jun 2004

Characteristics of Survivors vs. Deaths Characteristics of Survivors vs. Deaths among 400among 400--500gm 500gm (VON:1996(VON:1996--2000)2000)

ELBW 28d survival in the 1990’sELBW 28d survival in the 1990’sEPICure Study (Mar ‘95 EPICure Study (Mar ‘95 –– Dec ‘95)Dec ‘95)

All ELBW births in UK (276 Maternity Hosp)All ELBW births in UK (276 Maternity Hosp)

4004 births recorded ≤ 25 (204004 births recorded ≤ 25 (20--25) wk GA25) wk GA•• <23wk GA<23wk GA : : 92% died in DR (median BWt=490gm)92% died in DR (median BWt=490gm)•• 23wk GA23wk GA : : 50% died in DR (median BWt=600gm)50% died in DR (median BWt=600gm)•• 24wk GA24wk GA : : 18% died in DR (median BWt=680gm)18% died in DR (median BWt=680gm)•• 25wk GA25wk GA : : 8% died in DR (median BWt=760gm)8% died in DR (median BWt=760gm)

811 admitted to NICU811 admitted to NICU

495/811 (61%) died before discharge495/811 (61%) died before discharge

55% deaths d/t withdrawal of care55% deaths d/t withdrawal of care

Costeloe K, et. al., EPICure Study Group, Pediatrics, 2000

Costeloe K, et. al., EPICure Study Group, Pediatrics, 2000

ELBW 28d Survival in the 1990’sELBW 28d Survival in the 1990’sEPICure Study (Mar ‘95 EPICure Study (Mar ‘95 –– Dec ‘95)Dec ‘95)

•• After improvements in NICU care, repeated After improvements in NICU care, repeated Epicure study in 2006.Epicure study in 2006.

•• 4008 4008 eligible births at <27 wks (22eligible births at <27 wks (22--26 6/726 6/7thth wk)wk)

•• 17% terminations and 22% antepartum stillbirths17% terminations and 22% antepartum stillbirths

•• Outcomes reported for Outcomes reported for n=2180n=2180 (alive at onset of (alive at onset of labor, or delivered by c/s prior to onset of labor)labor, or delivered by c/s prior to onset of labor)

ELBW 28d survival after 2000ELBW 28d survival after 2000EPICure 2 (study period: 2006)EPICure 2 (study period: 2006)

Costeloe K, et. al., 2009 Pediatric Academic Society Meeting, Baltimore, MD

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22wk 23 wk 24 wk 25 wk 26 wk

Alive at labor onset or c/s) 258 393 462 515 552

Intra-partum stillbirth 110 75 51 25 13

Live birth 148 318 411 490 539

Neonatal death in DR128

(49%)118 (30%) 55 (12%) 21(4%) 7 (1.2%)

Admission to NICU 20 (7.7%) 200 (51%) 356 (77%) 469 (91%) 532 (96%)

Early neonatal death in NICU

9 86 87 64 56

Late neonatal death 5 33 60 47 37

Alive at 28 d 6 (2%) 81 (21%) 209 (45%) 358 (70%) 439 (80%)

ELBW survival to 28 daysELBW survival to 28 daysEPICure2 (2006)EPICure2 (2006)

Costeloe K, et. al., 2009 Pediatric Academic Society Meeting, Baltimore, MD

What is the 28 day survival rate for infants What is the 28 day survival rate for infants born at 24 weeks gestational age?born at 24 weeks gestational age?

<5% 25

%

45%

75%

0% 0%0%0%

:10

A.A. <5%<5%B.B. 25%25%

C.C. 45%45%

D.D. 75%75%

What is the data on outcomes of What is the data on outcomes of extremely low birth weight extremely low birth weight

infants? infants?

Population/SinglePopulation/Single--InstitutionInstitutionMORTALITYMORTALITY

Survival* between 23Survival* between 23--26wks GA 26wks GA (Univ Minnesota: 1986(Univ Minnesota: 1986--2000)2000)

n=1036 infants (1986-2000)

Hoekstra RE, et. al., Pediatrics, Jan 2004

*Among infants who survived to admission• Mean BWt = 744gm• Mean GA (wk) = 24.8wk GA• White: 83%• Multiple GA: 26%• C-section: 54%

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Hoekstra RE, et. al., Pediatrics, Jan 2004

Survival* between 23Survival* between 23--26wks GA 26wks GA (Univ Minnesota: 1986(Univ Minnesota: 1986--2000)2000)

Overall survival by GA between 1986 and 2000 (*among survivors to admission)

Avg=47%

Avg=66%Avg=80% Avg=86% • n = 1478 live born infants with BWt 500-999gm

• Single Perinatal Center (Case Western Reserve)

• Three epochs examined:

• Period I (1982-1989): n = 496

• Period II (1990 -1999): n = 749

• Period III (2000-2002): n = 233

• Improved 20 month CA survival only through 1990’s:

• Period I (1982-1989): 242/496 = 49%

• Period II (1990 -1999): 508/749 = 68%

• Period III (2000-2002): 165/233 = 71%

Wilson-Costello D, Pediatrics, Apr 2005 & Jan 2007

Survival between 500gmSurvival between 500gm--999gm 999gm (Case Western Reserve: 1982(Case Western Reserve: 1982--2002)2002)

P<0.01

NS

Survival between 500gmSurvival between 500gm--999gm 999gm (Case Western Reserve: 1982(Case Western Reserve: 1982--2002)2002)

Wilson-Costello D, Pediatrics, Jan 2007Piecuch, et al, Pediatrics, 2000

Survival between 24Survival between 24--28 wk GA28 wk GA(Univ of California San Francisco: 1990(Univ of California San Francisco: 1990--1994)1994)

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What is the data on outcomes of What is the data on outcomes of extremely low birth weight extremely low birth weight

infants? infants?

MORBIDITYMORBIDITY

Morbidity among 400Morbidity among 400--500gm500gmVermont Oxford Network (1996Vermont Oxford Network (1996--2000)2000)

Lucey, JF, et. al., Vermont Oxford Network, Lucey, JF, et. al., Vermont Oxford Network, Pediatrics,Pediatrics, Jun 2004Jun 2004

EPICure (1995) long term followEPICure (1995) long term follow--upupDo our assessment tools underestimate impairment?Do our assessment tools underestimate impairment?

6 year outcomes of UK infants born ≤ 25 wk GA.6 year outcomes of UK infants born ≤ 25 wk GA.

21% 21% of survivors showed cognitive and neurologic impairment of survivors showed cognitive and neurologic impairment by standardized testingby standardized testing

41% 41% showed cognitive and neurologic impairment compared showed cognitive and neurologic impairment compared to classmates.to classmates.

Disability was:Disability was:–– Mild: 34%Mild: 34%–– Moderate 24%Moderate 24%–– Severe 22%Severe 22%–– Disabling cerebral palsy 12%Disabling cerebral palsy 12%

Marlow, N, et. al., EPICure Study Group, New Eng J Med, Jan 2005

1995 2006 comments

Survival of admissions to d/c

40% 52%P<0.0001, sig incr b/t 24->25 wks (not

<24wk). Increased survival in first week.

% survivors with HC or cysts

15% 13% NS

% survivors on O2 at 36 wks

75% 74% NS

%survivors treated for ROP

13% 21%P= 0.008 – Not believed to be increase in ROP disease, but changes in screening

and treatment thresholds.

ComparingComparing outcomes by periodsoutcomes by periods19951995 (EPICure)(EPICure) vs. vs. 2006 2006 (EPICure2)(EPICure2)

Costeloe K, et. al., Costeloe K, et. al., 2009 Pediatric Academic Society Meeting, Baltimore, MD2009 Pediatric Academic Society Meeting, Baltimore, MD

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Comparing outcomes by periodsComparing outcomes by periodsIntact survival in the Intact survival in the 1990’s 1990’s (Case Western Reserve)(Case Western Reserve)

WilsonWilson--Costello, Hack M, et al. Costello, Hack M, et al. PediatricsPediatrics, Apr 2005, Apr 2005 WilsonWilson--Costello, Hack M, et al. Costello, Hack M, et al. PediatricsPediatrics, Jan 2007, Jan 2007

Comparing outcomes by periodsComparing outcomes by periodsIntact survival after Intact survival after 20002000 (Case Western Reserve)(Case Western Reserve)

(31.8%)(40.8%)

(50.2%)

WilsonWilson--Costello, Hack M, et al. Costello, Hack M, et al. PediatricsPediatrics, Jan 2007, Jan 2007

Comparing outcomes by periodsComparing outcomes by periodsIntact survival after 2000 Intact survival after 2000 (Case Western Reserve)(Case Western Reserve)

Outcomes at 18Outcomes at 18--24 months of ELBW 24 months of ELBW 400400--1000gm 1000gm (VON:2000(VON:2000--2005)2005)

Vermont Oxford NetworkVermont Oxford Network

Cohorts 1999 2000 2001 2002 2003 2004 2005

Infants eligible 1840 1199 4218 1235 1135 1310 1729

Evaluated at18-24 mos 1080 695 2446 744 689 773 873

Severe Disability among survivors

32% 31% 31% 27% 28.8% 31.1% 24.6%

* Severe disability: Severe disability: bilat blindness, hearing impairment req amplification, inability to walk without support, CP, or Bayley MDI <70.

2001-2005 combined cohort for 400-1000gm BWt• eligible infants = 6,636 • evaluated at 10-24mos = 3745 • severe disability (among survivors) = 31.5%

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University of California, San FranciscoUniversity of California, San FranciscoWilliam H. Tooley Intensive Care NurseryWilliam H. Tooley Intensive Care Nursery

HighHigh--Risk FollowRisk Follow--up Clinic Outcomesup Clinic Outcomes

� 24 weeks24 weeks� 60% survival� 21% “intact survival” with normal/borderline cognition

� 25 weeks 25 weeks � 70% survival � 38% intact

� 26 weeks 26 weeks � 75% survival� 40% intact

� 28 weeks 28 weeks � >85% survival,

� follows bell-shaped curve

What is the “intact survival” (at >18 month What is the “intact survival” (at >18 month followfollow--up) for ELBW infants born at 25wks GA?up) for ELBW infants born at 25wks GA?

10-20

%

35-45

%

60-7

0%

75-8

5%

0% 0%0%0%

:10

A.A. 1010--20%20%B.B. 3535--45%45%C.C. 6060--70%70%D.D. 7575--85%85%

Predicting outcomes?Predicting outcomes?

Tyson JE, NICHD Neonatal Rch Network. Tyson JE, NICHD Neonatal Rch Network. New Eng J Med, New Eng J Med, 20082008

• Neonatal Research Network of the NICHD• 4446 infants born at 22 to 25 weeks' gestation • Related risk factors to likelihood of:

• survival• survival w/o profound ND impairment• survival w/o ND impairment at 18-22 months

• Multivariate analysis found improved outcomes associated with four factors (independent of GA): antenatal steroids, female sex, singleton birth and higher birth weight.

AAP and ACOG StatementsAAP and ACOG Statements-- ACOG Practice Bulletin: No 38, Sept 2002, Obstet Gynecol, 2002, SeptACOG Practice Bulletin: No 38, Sept 2002, Obstet Gynecol, 2002, Sept

-- Perinatal Care at the Threshold of Viability, Committee Opinion No. 163Perinatal Care at the Threshold of Viability, Committee Opinion No. 163, , Pediatrics,Pediatrics, 19951995

“Perinatal Care and the Threshold of Viability”“Perinatal Care and the Threshold of Viability”

Emphasizes need to inform parents of survival Emphasizes need to inform parents of survival

rates and outcomes to clarify risks and benefits rates and outcomes to clarify risks and benefits of different approaches to treatment.of different approaches to treatment.

Stresses importance of keeping parents aware Stresses importance of keeping parents aware

throughout the infant’s course of the potential throughout the infant’s course of the potential

complications of prolonged ICU care.complications of prolonged ICU care.

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ConclusionsConclusions•• Survival of ELBW infants (<1000gm) has gradually improved Survival of ELBW infants (<1000gm) has gradually improved

in last 20 years.in last 20 years.

•• Similar improvements in neurodevelopmental outcomes Similar improvements in neurodevelopmental outcomes lagged in the 1990’s but maybe improving since 2000. lagged in the 1990’s but maybe improving since 2000.

•• However, cognitive and neurologic impairment is still However, cognitive and neurologic impairment is still common among excommon among ex--ELBW children at school age and ELBW children at school age and current assessment tools may underestimate impairments in current assessment tools may underestimate impairments in exex--ELBW children.ELBW children.

•• Discussions with parents must include the most up to date Discussions with parents must include the most up to date information on survival and outcomes to properly weigh risks information on survival and outcomes to properly weigh risks and benefits in the current era.and benefits in the current era.

Thank YouThank You