Outcome for Extremely Premature Infants A 400 Gram Female Infant - - PowerPoint PPT Presentation

A 400‐Gram Female Infant Delivered at 24 and 4/7 Weeks.

Outcome for Extremely Premature Infants Andrew T. Costarino, M.D. SPA October 2013

Photo: N Engl J Med 2013;368:2349‐2351.

SPA October 2013

P t Bi th i t

• Preterm: Birth prior to:

– 37 completed weeks of gestation f th 259 d i th fi t d f – or fewer than 259 days since the first day of a woman’s last menstrual period.

• Sub‐divided on gestational age:
• Sub‐divided on gestational age:
• Late preterm

(34 to <37 weeks)

• Moderate preterm (32 to <34 weeks)

Moderate preterm (32 to <34 weeks)

• Very preterm

(28 to <32 weeks)

• Extremely preterm (<28 weeks)

Extremely preterm (<28 weeks) W ld H lth O i ti 1977 World Health Organization: 1977

Preterm Birth USA, 2011

Total Births 3 953 590 Total Births ‐ 3,953,590 Total Preterm Births ‐ 463,756 Preterm Birth Rate – 11.73% Associated Infant Deaths – 10,991

440 000 495,000 275 000 330,000 385,000 440,000

34 ‐ 36 wks 8.28% (327,357) 32 ‐ 33 wks 1.52% (60,095)

165,000 220,000 275,000

28 ‐ 31 wks 1.2% (47,443)

55,000 110,000

<28 wks .73% (28,861)

Preterm

CDC, National Center for Health Statistics Final Data 2011

Preterm Birth USA

Preterm Birth Rate 2012: 11 5% Preterm Birth Rate 2012: 11.5%

Twin and triplet birth rates: USA, 1980–2010 Hamilton BE et al. Pediatrics 2013;131:548‐558

VLBW Outcomes of the NICHD Neonatal Network

90 100

Survival by GA

50 60 70 80 90

val (%)

20 30 40 50

Surviv

10

Gestational Age

Hack M et al. Pediatrics 1991;87: 587‐597

ELBW Infants Outcome

Innovation Time CPAP, MV techniques 1980’s Exogenous Surfactant Early 1990’s Antenatal Steroids Mid/Late 1990’s Avoiding Postnatal Steroids Early 2000’s Targeted Oxygen Therapy Mid 2000’s Systematic Care/Experience Continuous

Outcome Studies ELBW Infants

Country Country Year Year Sponsor Sponsor

1 USA 1987 NICHD 2 USA 1992 NICHD 3 Australia 1992 Victoria Collaborative Study Group 4 Belgium 1992 EPIBEL Study Group 5 UK/Ireland 1995 EPIcure Study Collaborative 6 France 1997 EPIPAGE Study Group 7 USA 2003 Vermont Oxford 8 USA 2004 NICHD 9 Australia 2005 Victoria Collaborative Study Group 10 Belgium 2005 EPIBEL Study Group 10 Belgium 2005 EPIBEL Study Group 11 Japan 2005 Japanese Neonatal Network

ELBW Infants Survival

80 100 26 weeks 60

cent

25 weeks 24 weeks 40

Perc

23 weeks 22 weeks 20

1 2 3 4 5 6 7

ELBW Infants Survival

80 100 26 weeks 60

cent

25 weeks 24 weeks 40

Perc

23 weeks 22 weeks 20

1 2 3 4 5 6 7

ELBW Morbidity ELBW Morbidity Risk Risk 95% CI 95% CI

Acute/NICU Acute/NICU Any ROP Severe ROP Severe ROP IVH (Grade III‐IV) Surgical NEC g Chronic Problems BPD (O2 at 36 weeks) BPD (clinical) Blindness Hearing loss Cerebral Palsy Cognitive Delay

Cross KW. Lancet 1973;ii:954‐956

ELBW Oxygen Trials

• USA: “SUPPORT” N=1316

– NEJM 2010;362:1959 NEJM 2010;362:1959. – NEJM 2012;367:2995.

• Canada/Europe: “COT” N=1201
• Canada/Europe: COT N=1201

– JAMA. 2013;309:2111.

• UK/Australia/NZ: “BOOST” N=2448
• UK/Australia/NZ: “BOOST” N=2448

– NEJM 2013;368: 2094‐2104

ELBW Morbidity ELBW Morbidity Risk Risk 95% CI 95% CI

Acute/NICU Acute/NICU Any ROP 63.7 60.6 – 66.6 Severe ROP 12.3 11.3 – 13.3 Severe ROP IVH (Grade III‐IV) 14.1 13.1 – 15.2 Surgical NEC 10.1 9.3 – 11.0 g Chronic Problems BPD (O2 at 36 weeks) 42.2 40.4 – 43.9 BPD (clinical) 38.7 36.9 – 40.5 Blindness 0.8 0.36 – 1.62 Hearing loss 3.1 2.1 – 4.4 Cerebral Palsy 6.1 4.7 – 7.7 Cognitive Delay 7.4 5.2 – 9.4

ELBW Morbidity: Neurodevelopmental

• Domains of Neurodevelopmental disabilities

Domains of Neurodevelopmental disabilities. –Motor (cerebral palsy) G

• Gross motor
• Fine motor

–Cognition –Speech and language Speech and language, –Personal‐social A i i i f d il li i –Activities of daily living.

ELBW Morbidity: Cerebral Palsy

Cerebral Palsy

A i di bili d d h

• A non‐progressive motor disability due to damage to the

motor control centers of the developing brain. D d i t ti t bi th ft bi th

• Damage can occur during gestation, at birth or after birth

up to about 3 years of age.

• Affects about 2 5/1 000 children in the US
• Affects about 2.5/1,000 children in the US.
• Prematurely born infants are at increased risk for CP.
• Close to half of children with CP were born prematurely.
• Often used as a marker for over‐all neurologic outcomes

associated with prematurity.

Risk of Cerebral Palsy Risk of Cerebral Palsy

45

Pooled Risk Estimate 10.4 95% CI: 7.3 – 13.5

30 35 40

urvivors

15 20 25

cent of su

5 10

Perc

ELBW Morbidity

Reid SM et al. Dev Med Child Neurol 2011; 53:907‐912.

ELBW Morbidity ELBW Morbidity Risk Risk 95% CI 95% CI

Acute/NICU Acute/NICU Any ROP 63.7 60.6 – 66.6 Severe ROP 12.3 11.3 – 13.3 Severe ROP IVH (Grade III‐IV) 14.1 13.1 – 15.2 Surgical NEC 10.1 9.3 – 11.0 g Chronic Problems BPD (O2 at 36 weeks) 42.2 40.4 – 43.9 BPD (clinical) 38.7 36.9 – 40.5 Blindness 0.8 0.36 – 1.62 Hearing loss 3.1 2.1 – 4.4 Cerebral Palsy 6.1 4.7 – 7.7 Cognitive Delay 7.4 5.2 – 9.4

Logistic regression: O d/ CP Outcome: mod/severe CP Risk factors: PVL Grade 3‐4 IVH BPD Postnatal Steroids Postnatal Steroids Male Gender

Vohr BR et al. Pediatrics 2005;116:635‐643

ELBW Morbidity: Cognitive Delay ELBW Morbidity: Cognitive Delay

• Bayley Scales of Infant Development, (designed for children aged 0

to 3 years) to 3 years).

• The first developed in the 1960’s
• Behavioral/play examination raw score converted to composite
• Behavioral/play examination ‐ raw score converted to composite

scale then referenced to normative values.

• The scores have a normal distribution with a mean of 100 and

The scores have a normal distribution with a mean of 00 and standard deviation of 16.

• Revised and in 1993 = Bayley II comprised of 2 parts:

– MDI (Mental Developmental Index) cognitive and language – PDI (Psychomotor Developmental Index) motor skills. ( y p )

Bayley Developmental Index in Premature Survivors

110 120 SD) Advanced Development (Green dash) 100 110 ex (mean± Normal (Pink shaded) 90 mental Inde 70 80 Developm Significantly Delayed Development (Red dash) 60

Period I Period II

Hack M. et al. Pediatrics 1996; 98: 931‐937

Cognitive Impairment

Moore T et al. Brit Med J. 2012;345:e7961

ELBW Morbidity: Cognitive Delay

80

Pooled Risk Estimate 25.2, 95% CI: 20.4 – 30.5

60 70 40 50

Percent

10 20 30

P

10

Logistic regression for MDI <70, ORs and 95% CIs.

Logistic regression Logistic regression Outcome: cognitive delay Risk factors: PVL Grade 3‐4 IVH Early 90’s EPOCH y Postnatal Steroids Male Gender

Vohr BR et al. Pediatrics 2005;116:635‐643

ELBW Morbidity ELBW Morbidity Risk Risk 95% CI 95% CI

Acute/NICU Acute/NICU Any ROP 63.7 60.6 – 66.6 Severe ROP 12.3 11.3 – 13.3 Severe ROP IVH (Grade III‐IV) 14.1 13.1 – 15.2 Surgical NEC 10.1 9.3 – 11.0 g Chronic Problems BPD (O2 at 36 weeks) 42.2 40.4 – 43.9 BPD (clinical) 38.7 36.9 – 40.5 Blindness 0.8 0.36 – 1.62 Hearing loss 3.1 2.1 – 4.4 Cerebral Palsy 6.1 4.7 – 7.7 Cognitive Delay 7.4 5.2 – 9.4

ELBW Morbidity ELBW Morbidity Risk Risk 95% CI 95% CI

Acute/NICU Acute/NICU Any ROP 63.7 60.6 – 66.6 Severe ROP 12.3 11.3 – 13.3 Severe ROP IVH (Grade III‐IV) 14.1 13.1 – 15.2 Surgical NEC 10.1 9.3 – 11.0 g Chronic Problems BPD (O2 at 36 weeks) 42.2 40.4 – 43.9 BPD (clinical) 38.7 36.9 – 40.5 Blindness 0.8 0.36 – 1.62 Hearing loss 3.1 2.1 – 4.4 Cerebral Palsy 6.1 4.7 – 7.7 Cognitive Delay 7.4 5.2 – 9.4

Short‐term outcome at discharge for infants with a GA of 24 to 26 wks

Vanhaesebrouck P et al. Pediatrics 2004;114:663‐675

Died

27

Died Severe Disability

40

Disability No disability

12

Gestational Age

12

Gestational Age Birth weight Anenatal Steroids Gender Multiple/Singleton Gestation

Tyson JE et al. N Engl J Med 2008; 358:1672‐168

http://www nichd nih gov/about/org/der/branches/ppb http://www.nichd.nih.gov/about/org/der/branches/ppb /programs/epbo/pages/epbo_case.aspx

ELBW Outcome ELBW Outcome

• Premature birth significant cause of infant mortality and

child morbidity

• US Premature birth rate decreasing now 11.5%
• Viability (50% survival) in developed countries = 23‐24

wks GA

• The smallest infants are at significant risk of death and

disability % li – 30‐50% Mortality – Survivors 40‐80% significant morbidity

ELBW Outcome

• CPAP/MV and surfactant increased survival 1980’s early
• CPAP/MV and surfactant increased survival 1980 s early

90’s

• Antenatal steroids improved mortality and morbidity in
• Antenatal steroids improved mortality and morbidity in

late 90’s

• Avoiding postnatal steroids improved morbidity

Avoiding postnatal steroids improved morbidity.

• Each week of GA and each 100 grams birth weight offers

a significant improvement in survival and morbidity a significant improvement in survival and morbidity

• Target O2 to SpO2 of >90%
• Girls do better than boys

Girls do better than boys

• Hospital discharge on the EDC if complications are few.
• Follow up for developmental learning behavioral and
• Follow up for developmental, learning, behavioral and

social problems.

5‐18% is the range of preterm birth rates across 184 countries of the world the world >80% of preterm births

• ccur between 32‐37

weeks of gestation and g most of these babies can survive with essential newborn care

World Health Organization: Born too soon: the global action report on preterm birth. WHO Press, Geneva, Switzerland 2012

Outcomes of Extremely Low Birth Weight Infants

100 0

Survival per Live Birth Survival per NICU Admission

60 0 80.0 100.0

ercent

1982‐88 1990‐92

60 0 80.0 100.0

rcent p

1982‐88 1990‐92

20 0 40.0 60.0

Survival Pe

20 0 40.0 60.0

Survival Per

1990‐92

0.0 20.0

<50 500 600 700

0.0 20.0

S 00 0‐599 0‐699 0‐749

Hack M et al. Pediatrics 1996;98: 931‐937

Premature Birth Global Health Problem

• 2010: 1/10 births world

wide = 15 million.

• Mortality:

Mortality: – >1 million deaths. – Biggest contribution to infant mortality. y – #2 cause of death under 5 years.

• Morbidity: risk for lifetime of

disability – Motor, sensory, cognitive. C t i 50% f – Component in 50% of long term morbidity.

• Preterm birth increasing in

most countries most countries.

Liu, L. et al. Lancet 2012; 379: 2151‐2161

Outcome for Extremely Premature Infants Outcome for Extremely Premature Infants

• Necessary Definitions
• Overview

– Global – National

• Survival

Survival

• Morbidity

NICU – NICU – Infancy/Young childhood

Term Definition Time Units

l l d b h l d Gestational age Time elapsed between the first day of the last menstrual period and the Completed weeks p day of delivery Chronological age Time elapsed since birth Days, weeks, th months, years Postmenstrual age Gestational age + chronological age Weeks chronological age Corrected age Chronological age reduced by the number of weeks Weeks, months born before 40 weeks of gestation.

• Small for gestational age (SGA):

– Weight less than 10th percentile at given fetal GA. – By definition <2,500 grams at term birth. y , g – Does not distinguish among the various etiologies.

• Large for gestational Age (LGA):

Large for gestational Age (LGA):

– Greater than 90th percentile for duration of gestation. By definition >4 500 grams at term birth – By definition >4,500 grams at term birth – Associated with gestational diabetes, excessive maternal weight gain. maternal weight gain. – More of an issue in the term and late premature infant compared to very premature.

WHO, March of Dimes “Born Too Soon” Global Action Report 2012

• Live Birth:

– ‘‘Live Birth’’ complete expulsion p p – After expulsion, breathes, or shows any other evidence of life – Heartbeats distinguished from transient contractions; R i ti di ti i h d f fl ti i t – Respirations distinguished from fleeting respiratory gasps.

• Fetal Death: Also Stillbirth

– ‘‘Fetal death’’ means death prior to the complete expulsion p p p – The death is indicated by: fetus does not breathe or show any other evidence of life, Heartbeats distinguished from transient cardiac contractions; – Heartbeats distinguished from transient cardiac contractions; – Respirations distinguished from fleeting respiratory gasps.

• Stillbirth international comparison definition:

– Birth Weight ≥ 1000 grams or ≥ 28 weeks completed gestation.

• Planned Terminations: Excluded from these definitions and totals.

WHO 1950, revised in 1988 (CDC and National Center for Health Statistics. 1997

Infant, neonatal, and post-neonatal mortality rates: United States, 2005–2010 (final) and 2011 (preliminary). ( ) (p y)

Hamilton BE et al Pediatrics 2013;131:548 558 Hamilton BE et al. Pediatrics 2013;131:548‐558

• Gestation Age (GA):

– Age of the fetus as length‐of‐pregnancy in weeks – Age of the fetus as length‐of‐pregnancy in weeks – Measured from the first day of the last menstrual period. – Recorded as completed weeks and is never rounded up.

• Estimated date of confinement (EDC): Also “due date”
• Estimated date of confinement (EDC): Also due date

– 40 weeks added to the LMP – Estimated day infant will be born.

• Postmenstrual age (PMA):
• Postmenstrual age (PMA):

– Gestational age plus the time elapsed after birth chronological age – Recorded in weeks Used during the perinatal period beginning after the day of birth – Used during the perinatal period beginning after the day of birth. – Incorrect term: “post‐conceptual” age.

• Corrected age: Also “adjusted age”

Ti f th EDC – Time from the EDC. – Used to describe children up to 3 years who were born preterm. AAP Committee on Fetus and Newborn. PEDIATRICS 2004;114:1362

L Bi h W i h (LBW)

• Low Birth Weight (LBW):

– <2,500 grams birth weight.

• Very Low Birth Weight (VLBW):

– ≤1,500 grams.

• Extremely Low Birth Weight (ELBW):

– <1,000 grams. <1,000 grams. – Less consistently defined – Designated as 1 000 grams 800 grams 750 grams Designated as 1,000 grams, 800 grams, 750 grams depending on study or reporting agency.

Vanhaesebrouck P et al. Pediatrics 2004;114:663‐675

Preterm Birth USA

CDC and Prevention, National Center for Health Statistics

ELBW Morbidity

60.6/1,000 Live births 39.6/1,000 Live births

Platt MJ et al. Lancet 2007; 371: 43‐50.