the limits of viability: how small is too small? istvan seri m.d., ph.d. usc division of neonatal...

The Limits of Viability:

How Small Is Too Small?

Istvan Seri M.D., Ph.D.

USC Division of Neonatal MedicineWomen’s and Children’s Hospital

LAC/USC Medical Center and Children Hospital Los Angeles

Keck School of MedicineUniversity of Southern California

Los Angeles, CA

1960’s - 30-31 weeks

1980’s - 26-27 weeks

2000 - 24 weeks

The Limits of Viability:How Small Is Too Small?

Gestational age at which a newborn had a 50% chance of survival

Too smallToo immature

Comfort Care Only

Too bigToo mature

Unreasonable Mandatory

Active Intervention

Gray ZoneGray Zone

??? Intervention ?????? Intervention ?????? Intervention ?????? Intervention ???


Per

cen

t S

urv

ival

by

Ges

tati

onal

Age

0

10

20

30

40

50

60

70

80

90

22 23 24 25 26

Gestational Age (weeks)

USA/CND studies using surfactant 1990-2001

0-12%

0-55%

23-62%

Percent Survival by Gestational Age


Per

cent

Su

rviv

al b

y B

irth

Wei

ght

01020304050607080

401-500 501-600 601-700 701-800

Birthweight Ranges (g)

1990's

1-38%

16-37%

Percent Survival by Birth Weight


Nu

mb

er

of

Pati

en

ts

0

500

1000

1500

2000

2500

3000

3500

4000

4500

100% 52% 48% 30% 17%

All NeonatesDR DeathsAdmit to NICUNICU DeathsSurvived till D/C


Lucey et al, Pediatrics 113:1559, 2004

Percent

Outcome of Neonates with Birth Weights of 401-500 gGestational age = 23.3 ±2.1 weeks




Total Neonates RegisteredN = 4172 (100%)

Died in Delivery RoomN = 2186 (52%)

Survived DR to NICUN = 1986 (48%)

Survival StatusUnknown N = 43 (1%)

Survived to NICU D/CN = 690 (17%)

Died in NICUN = 1253 (30%)

Gestational Age = 25.3 ±2 weeks




Compared to patients who died in the DR, neonates who

survived to be admitted to the NICU were more likely to

1. Be female (58% vs 49%)

2. Be small for gestational age (56% vs 11%)

3. Have received prenatal steroids (61% vs 12%)

4. Have been delivered via cesarean section (55% vs 5%)

Synnes et al, 1994

05

101520253035404550

% Survival

400 500 600 700

Birth Weight (g)

23 wks 24 wks 25 wks

Percent Survival by Gestational Age and Birth Weight


0102030405060708090

100

Admission

Day 1 Week 1 Month1 Month 6

Survival

22 wks23 wks24 wks25 wks

%

Burdens of Prolonging Support in Infants at the Limits of Viability


Infants born <23 weeks too immature to survive


Comfort care only

0

10

20

30

40

5060

70

80

Survival(%)

23 wks 24-25 wks

Compromise No CompromiseBatton et al, 1998

Effect of Fetal Compromise on Survival


0

10

20

30

40

50

60

199119921993199419951996199719981999

501-750 g751-1000 g1001-1500 g

Vermont-Oxford Network (362 Institutions)

Pediatrics 110:143, 2002

Gestational Age-Dependent Mortality (1991-1999)


0

10

20

30

40

50

60

70

80

90

100

501-600

601-700

701-800

801-900

901-1000

1001-1100

1101-1200

1201-1300

1301-1400

1401-1500

1977-'811982-'851986-'901991-'951996-'00

Parkland Memorial Hospital, Dallas, TXKaiser et al, J Perinatol 24:343, 2004

Birth Weight-Specific Survival of VLBW Neonates (1977-2000)


Decision-Making at the Threshold of Infant

Viability

Estimating Survival & Intact Survival

GA BW Survival Intact Survival*(weeks) (g) ( % ) ( % )

23 600 50 % 25 %

24 700 70 % 70 %

25 800 80 % 80 %

26 900 90 % 70 %

27 1000 95 % 80 %

GA BW Survival Intact Survival*(weeks) (g) ( % ) ( % )

23 600 50 % 25 %

24 700 70 % 70 %

25 800 80 % 80 %

26 900 90 % 70 %

27 1000 95 % 80 %* Among Survivors

Infants born >25 weeks are mature enough


Full support warranted

Target range for “Gray Zone” based on survival:

23-24 6/7th weeks and 500-600 g

What are the complications and outcome data of premature neonates

in the “Gray Zone”?


0102030405060708090

23 24 25

Gestational Age

Allen, 1993Cooke, 1996El-Metwally, 2000Hussain,1998

%

Percent Severe Head Ultrasound Abnormalities by Gestational Age


0102030405060708090

23 24 25

Gestational Age

Epicure, 2000Cooke, 1996El-Metwally, 2000Kilpatrick, 1997Bardin, 1996

%

Percent Chronic Lung Disease at 36 weeks by Gestational Age at Birth


0

10

20

30

40

50

60

70

80

22 23 24 25 26 27

Survival Intact Survival

Doyle et al Pediatrics, 2001

%

Percent Survival and Intact Survival by Gestational Age


Bottoms et al, NICHD Network, 1997

0

10

20

30

40

50

60

70

80

401-500 501-600 601-700 701-800

Survival Intact Survival

%

Percent Survival and Intact Survival by Birth Weight


The Limits of ViabilityImpact of BPD, Brain Injury and ROP on 18-

Month Outcome of ELBW Infants

Outcome Variable

Odds Ratio 95 % CI

BPD 2.4 1.8 – 3.2

Brain Injury 3.7 2.6 – 5.3

Severe ROP 3.1 1.9 – 5.0

Schmidt et al: JAMA 289:1121, 2003

These 3 common neonatal morbidities strongly predict the risk of later death or disability

Overall probability of poor outcome at 18 m (35%)

The Limits of ViabilityImpact of BPD, Brain Injury and ROP on 18-Month

Outcome of ELBW Infants

Schmidt et al: JAMA 289:1121, 2003

These 3 common neonatal morbidities strongly predict the risk of later death or disability

VON 2000

The Limits of ViabilityPulmonary Outcome

VON 2000

The Limits of ViabilityIVH and PVL: Incidence by Birth Weight

The Limits of ViabilitySequelae of Prematurity (1)Sequelae of Prematurity (1)

Place of Birth and Mortality in Canadian NICUsPlace of Birth and Mortality in Canadian NICUs

15662158

28633485

9193

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

< 1 kg 1-1.499 1.5-1.9992-2.499 >2.5 kg

17 NICUs

Admits = 19,265

Period = 1996-97

Nu

mb

er

of

NIC

U A

dm

its

Birth Weight (kg)

Sankaran K et al; CMAJ 166:173-8, 2002

Non-SPC SPC*

Death (%) 16.9 14.3

BPD (%) 20.1 17.5

IVH-III-IV 15 8.4

ROP (Treated) 5.6 4.8

NEC 6.1 7.2

Warner et al; Pediatrics 2004; 113:35-41

* SPC=Subspecialty Perinatal Center

The Limits of ViabilityPlace of Birth and Mortality in Infants with Birth Weight of 500-Place of Birth and Mortality in Infants with Birth Weight of 500-

1499 g1499 g

Gestational Age (weeks)

Adverse Outcome(Died or abnormal at 2

years)

23 – 24 92%

25 64%

26 35%

27 – 32 18%

Rijken et al; Pediatrics 2003; 112:351-58

The Limits of Viability

Survival and 2-year Outcome in Infants <27 wks (1996-

1997)

Hoekstra et al; Pediatrics 2004; 113:e1-e6

Gestational Age

(weeks)

Survival (%)

% Normal at 47.5 months

(n=675)

% Normal at 8 years (n=147)

23 66 52 33

24 81 59 55

25 85 66 67

26 93 66 65

The Limits of Viability Survival and Outcome of ELBW infants born at 23-26

weeks (1986-2000)

Hoekstra et al; Pediatrics 2004; 113:e1-e6


Factors Affecting Outcome of ELBW infants at 47.5 Months of Age (1986-

2000)

Problems with predicting long-term outcome

Adverse medium-term neurodevelopmental outcomes in ELBW infants

correlate with severe brain injury, CLD, NEC, steroid use for CLD, male

gender (Vohr et al, 1999)

However, long-term neurodevelopmental outcomes do not correlate well

with these predictors and maternal education and home environment are

more important than all other factors except severe brain injury


Outcome of ELBW Infants - NICHD American Experience

Patient population of 1126 infants (BW = 501 - 800 g)

Females have a survival advantage of 90 g

SGA neonates had a survival advantage of 57 g

Antenatal steroids confer a survival advantage of 67 g

Tyson et al JAMA 1996; 276:1645


Odds of Survival between 23 and 246/7 weeks

Chance of survival improves by 2% a day during 23 to

26 weeks gestational age

Overall, 50% survive and 50% of the survivors are

handicapped (the “50 - 50” rule)


Recent survival data (especially on non-compromised ELBW neonates)

Lower incidence of severe ROP, CLD and/or severe head ultrasound

abnormalities

Overall “intact” survival has increased from <10% to > 40%

Outcome still very uncertain for individual patient especially at 23 weeks

gestational age

The Gray Zone: 23 - 24 6/7 weeks gestation and 500 - 600 grams


Three approaches to care

1. Wait Until Certainty Approach Treatment begins on every infant thought to have any

chance of survival, wait until all information is in before deciding whether continuing care is the right decision (eg: USA)

2. Statistical ApproachDetermine categories of patients in which treatment may be limited or withheld (eg: Sweden)

3. Individualized Approach (eg: UK)

Clin Perinatol, 1996


Decision Making at The Threshold of Infant Viability Decision Making at The Threshold of Infant Viability

<23 wks

Comfort Care Only

25 wks

Unreasonable Mandatory

Full Critical Care

Gray ZoneGray Zone23-24 6/7 wks and 500-600 g23-24 6/7 wks and 500-600 g

Extent of active intervention based on condition and response

Parents indicate definite wishes for non-active intervention

(importance of counseling regarding impact of initial condition/perinatal stress on outcome)

Parents desire active intervention or defer to medical judgement

Follow parents wishes, unless evidence parents not working in best interest of the baby

The Limits of Viability: Decision-Tree

The Limits of Viability: Decision-Tree

500g* or< 23wk

Gray Zone23 - 246/7 wk and

500 - 599g

600gor 25wks

Heart rate

Low or Absent

Present >40-50

Bag/Intubate

Can’t intubate orpoor response (HR < 60/min

for 5mins)

Discontinue interventions& initiate comfort care

measures

HR = 60 - 100/min

Consider brief CPR, drugs and bolus fluids x1

Poor response

HR > 100/min

Give surfactant;insert lines;check ABG;start fluids

good response

Transfer to NICU

NICU CareOngoing evaluation

Parents desire active management

carry on, set limits

No resuscitationInitiate comfortcare measures

Initiate resuscitationClinical course willdictate management

Poor clinical status

* The occasional infant <500g BW (usually IUGR), who is vigorous at birth may warrant active intervention

Decision-Making at the Threshold of Infant Viability


• The algorithm assumes appropriate antenatal counseling

• Gestational age should be determined antenatally

• Birth weight must be obtained at the time of delivery

• At each stage of resuscitation, the prognosis for reasonable outcome should be reevaluated

• Parental wishes regarding extent of intervention in the gray zone should be honored until parents except their baby’s fate



Decision-Making at the Threshold of Infant ViabilityDecision-Making at the Threshold of Infant Viability

Relative weighting of parental, clinician and societal views of active Relative weighting of parental, clinician and societal views of active

interventionintervention with increasing gestational agewith increasing gestational age

Rel

ativ

e W

eigh

tin

g

22 282523 24 26 27

Parents Clinicians Society

Gestational Age at Birth

Questions?Questions?

Limits of Viability

the limits of viability: how small is too small? istvan seri m.d., ph.d. usc division of neonatal...

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