eduardo bancalari md university of miami miller school of ... · survival to discharge according to...

Neonatología: Desafíos Actuales

Eduardo Bancalari MD

University of Miami Miller School of Medicine

Congreso del Centenario

Sociedad Argentina de Pediatria

Buenos Aires 2011

Newborns <1000gUM – JMMC 1999-2001

294 births <1000g

18.990 livebirths 115 deaths

63 deaths <1000g1.54% of all births 54.78% of all deaths

Preterm Birth in the United States 1996-2007

March of Dimes

• Prematurity:

Border of viability

Survival to discharge according to GA among 9575 VL BW infants born in NICHD NRN centers between January 1, 2003, and December 31, 2007.

Stoll B J et al. Pediatrics 2010;126:443-456

Survival by Gestational Age2002-2006 U of M – JMMC

0

10

20

30

40

50

60

70

80

90

100

<23 23 24 25 26 27 28 29 30 31 32 >32

(%)

SU

RV

IVA

L

GESTATIONAL AGE (wks)

N=30

198184146

122

61

214 2949

107

150

110

84

Survival by Birthweight2002-2006 U of M – JMMC

0

10

20

30

40

50

60

70

80

90

100

<500 500-600 601-700 701-800 801-900 901-1000 1001-1250 1251-1500 >1500

(%)

SU

RV

IVA

L

BIRTHWEIGHT (g)

N=60

235119

118

125

122

269 3178

128

Desafíos clínicos actuales:

• Manejo respiratorio:

Soporte respiratorio invasivo vs no invasivo

Niveles de oxigenacion

• Hemorragia intracraneana- Leucomalacia

• Infecciones antenatales y hospitalarias

• Ductus Arterioso: Manejo agresivo vs

expectante

• Enteritis necrotizante

• Secuelas asociadas con prematurez extrema

Pulmonary insufficiency 167 (34.4%)

RDS ± IVH ± infection 150 (30.9%)

Late sequelae of ventilation 40 (8.2%)

Infection 40 (8.2%)

Intracranial bleeding 28 (5.8%)

Necrotizing enterocolitis 17 (3.6%)

Other 43 (8.9%)

No cause stated 15 (3.1)

More than 70% of deaths related to respiratory problems

Primary Cause of Death in 497 Infants 20Primary Cause of Death in 497 Infants 20Primary Cause of Death in 497 Infants 20Primary Cause of Death in 497 Infants 20----25wks GA 25wks GA 25wks GA 25wks GA (Excluding Those With Lethal Congenital Abnormalities)(Excluding Those With Lethal Congenital Abnormalities)(Excluding Those With Lethal Congenital Abnormalities)(Excluding Those With Lethal Congenital Abnormalities)

Costeloe K et al.The Epicure Study: Pediatrics: 106, 2000

Morbidity for VLBW infants born in the NICHD Neonat al Research Network between Jan. 1, 1997 and Dec. 31, 2002

501-750 g(n = 4046)

751-1000g(n = 4266)

1001-1250g

(n = 4557)

1251-1500g

(n = 5284)

501-1500g(n =

18,153)

Respiratory distress syndrome

71% 55% 37% 23% 44%

Pneumothorax 13% 6% 3% 2% 5%

O2 at 28 days 66% 37% 14% 5% 25%

Bronchopulmonary dysplasia

46% 33% 14% 6% 22%

Discharged on O 2 28% 18% 9% 4% 11%

Fanaroff, AA et al. Am. J Obstet Gynecol 2007; 196: 147.e1-147.e8

Morbidity for VLBW infants born in the NICHD Neonat al Research Network between Jan. 1, 1997 and Dec. 31, 2002

501-750 g(n = 4046)

751-1000g(n = 4266)

1001-1250g

(n = 4557)

1251-1500g

(n = 5284)

501-1500g(n =

18,153)

Grade I IVH 10% 11% 10% 11% 11%

Grade II IVH 7% 6% 4% 2% 4%

Grade III IVH 12% 9% 6% 4% 7%

Grade IV IVH 12% 5% 3% 1% 5%

PVL 4% 3% 2% 1% 3%

Fanaroff, AA et al. Am. J Obstet Gynecol 2007; 196: 147.e1-147.e8

Morbidity for VLBW infants born in the NICHD Neonat al Research Network between Jan. 1, 1997 and Dec. 31, 2002

501-750 g(n = 4046)

751-1000g(n = 4266)

1001-1250g

(n = 4557)

1251-1500g

(n = 5284)

501-1500g(n =

18,153)

Late-onset septicemia 44% 30% 17% 7% 22%

NEC, proven 11% 9% 5% 3% 7%

Growth Failure 97% 93% 87% 86% 91%

Fanaroff, AA et al. Am. J Obstet Gynecol 2007; 196: 147.e1-147.e8

Morbidity for VLBW infants born in the NICHD Neonat al Research Network between Jan. 1, 1997 and Dec. 31, 2002

501-750 g(n = 4046)

751-1000g(n = 4266)

1001-1250g

(n = 4557)

1251-1500g

(n = 5284)

501-1500g(n =

18,153)

Patent ductus arteriosus 49% 38% 23% 13% 29%

Indomethacin for PDA 84% 81% 75% 67% 79%

Surgery for PDA 29% 21% 10% 6% 19%

Fanaroff, AA et al. Am. J Obstet Gynecol 2007; 196: 147.e1-147.e8

Depressed Depressed Depressed Depressed ---- Poor resp effortPoor resp effortPoor resp effortPoor resp effort

ET tube IPPV

Surfactant if RDS

When stable extubate

to NCPAP or NIMV

Active Active Active Active ---- Good resp effort Good resp effort Good resp effort Good resp effort

Management of VLBWI in the DR

Start NCPAP

Deterioration,

Increasing FiO2,

PaCO2, Apnea

ET tube-IPPV-

Surfactant if RDS

When stable extubate

to NCPAP or NIMV

Stable-Continue

NCPAP

Support Trial – NICHD NRNNEJM, May 2010

1316 infants, 241316 infants, 241316 infants, 241316 infants, 24----28 weeks 28 weeks 28 weeks 28 weeks

Early CPAP vs. Intubation & Surfactant within 60 min of birthEarly CPAP vs. Intubation & Surfactant within 60 min of birthEarly CPAP vs. Intubation & Surfactant within 60 min of birthEarly CPAP vs. Intubation & Surfactant within 60 min of birth

CPAP ETT + Surfactant Relative Risk (CI)

Death or BPD 48.7 54 0.91 (0.83-1.01)

Death in 24-25 wks 23.9 32.1 0.74 (0.57-0.98)

Off mechanical ventilation at day 7 55.3 48.8 p <0.01

Required intubation 83.1 99.7 p < 0.0001

PN steroids 7.2 13.2 p < 0.0005

Supplemental Oxygen in Preterm Infants:

A Difficult Balancing Act

CNS hypoxia-damage

Multi organ/tissue hypoxia

Pulmonary vasculature

Ductus arteriosus

Impaired growth

Increased mortality

Lung injury-BPD

Retinal damage-ROP

CNS damage

Oxidative stress

Too MuchToo Little

1316 infants, 24-28 weeks gestational age, O2 saturation target : 85%-89% vs 91%-95%

SUPPORT Trial

Lower O2

Saturation

Group n/n (%)

Higher O2

Saturation

Group n/n (%)

Adjusted Relative

Risk (95% CI)

Severe ROP 43/483 (8.9) 95/514 (18.5) 0.51 (0.37, 0.71)

BPD (oxygen at 36 weeks) 203/540 (37.6) 265/568 (46.7) 0.82 (0.72, 0.93)

Death 130/654 (19.9) 107/662 (16.2) 1.27 (1.01,1.60)

SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. N Engl J Med. 2010;362:1959-1969.

UNANSWERED QUESTIONS

• What is the optimal range of oxygenation for

preterm infants?

• Does it differ at different gestational and

postnatal ages?

• Is there an FiO2that is safe for the preterm

lung or is 21% O2 is still too much?

Histologic chorioamnionitis in live-born preterm babies by

gestational age at RPAH from 1984 through 1999 (n = 3828 babies)

Antenatal Infection and Neonatal Outcome

• Fetal inflammatory response

• Preterm delivery

• Lung inflammation – pneumonia – BPD Accelerated maturation

More surfactant – Less RDSDisrupted alveolarization – BPD

• Disrupted CNS developmentWhite matter lesions – PVL Cerebral palsy

Morbidity for VLBW infants born in the NICHD Neonat al Research Network between Jan. 1, 1997 and Dec. 31, 2002

501-750 g(n = 4046)

751-1000g(n = 4266)

1001-1250g

(n = 4557)

1251-1500g

(n = 5284)

501-1500g(n =

18,153)

Late-onset septicemia 44% 30% 17% 7% 22%

Fanaroff, AA et al. Am. J Obstet Gynecol 2007; 196: 147.e1-147.e8

Stillbirth

5%

Neonatal

Death

62%

Serious

Morbidity

20%

Intact

Survival

13%

Stillbirth

0%

Serious

Morbidity

40%

Neonatal

Death

43%

Intact

Survival

17%

OB UNWILLING to perform cesarean delivery for fetal indications

OB WILLING to perform cesarean delivery for fetal indications

Bottoms SF, et al: Am J Obstet Gynocol 176:960, 1997

Neonatal outcome at 24 wks GA

Trends in neonatal morbidity and mortality for very low birthweight infants

Fanaroff, AA et al. Am. J Obstet Gynecol 2007; 196: 147.e1-147.e8

Stoll BJ et al. Pediatrics 2010;126:443-456

Survival Without Morbidity Extremely Preterm Infants

NICHD Neonatal Research Network

Clinical Practice Indicators and Survival Rates According to Birth Year for 9575 VLBW Infants Born in NRN Centers Between January

1, 2003, and December 31, 2007

Characteristics Percent Adjusted RR

(95% CI)P

2003

(N = 1919)

2004

(N = 1992)

2005

(N = 2032)

2006

(N = 1900)

2007

(N = 1732)

22 wk 0 0 0 0 0

23 wk 14 10 3 5 9

24 wk 5 10 10 8 11

25 wk 22 20 21 17 20

26 wk 32 38 34 31 34

27 wk 44 44 46 42 44

28 wk 58 55 62 55 54

All infants who survived to discharge 37 37 38 35 36 1.04 (1.02–1.06) <.001

Sequelae of Prematurity

• CNS damage post IVH-PVL

• BPD

• ROP

• Short gut post NEC

• Arterial hypertension/thrombosis

• Malnutrition

020

4060

80100

%

23 24 25 26 27 28

Gestational Age (wks)

NICHD NETWORK

Bronchopulmonary Dysplasia(O2 at 36 wks PMA)Years 2003-2007

0

4

8

12

16

20

24

28

32

36

40In

cide

nce

(%)

1994 1995 1996 1997 1998 1999 2000 2001 2002

Year

Unadjusted annual rates for GA <29 weeks (n = 1441)

BPD Severe BPD

Smith et al. J Pediatr. April 2005; 146(4):469-473

Retinopathy of Prematurity

(n=547 inborns BW:500-1000g, GA:23-32w, alive at 36wPMA, 1997-2002)

0

20

40

60

80

100

500-699g 700-1000g

Birthweight

%

All ROP Stage>=3 Laser Therapy

Clinical Practice and ROP

Chow L, et al: Pediatrics 111 (2):339, 2003

Bwt:500-749,750-999,

100-1249,1250-1500g

Infants 500 to 1500 g at CSMC (■) and VON ( ) for the years 1997 to 2001.

Chow, LC et al. Pediatrics 2003;111(2):339-345

Clinical Practice and ROP

Clinical Practice and ROP

Chow L, Wright K, Sola A: Pediatrics 111 (2):339, 2003

Malformaciones Congenitas

Causes of DeathBIRTHWEIGHT >2500g

JMH – 2005-2010N = 52

0

10

20

30

40

50

60

70

80

90

100

% O

F T

OT

AL

DE

AT

HS

CONG CHD ASP-PFC-MAS SEPS IVH NEC EXT PRE RF-RDS-PNEU BPD OTHER

FETAL INTERVENTIONSThe present and the future

• Immune hydrops, ascitis, hydrothorax• Premature rupture of membranes• TTTS• Urinary tract anomalies• Pulmonary cysts• Congenital diaphragmatic hernia• Hydrocephalus• Neural tube defects• CHD, aortic stenosis, pulmonary atresia

Errores Medicos-Seguridad del

Paciente

Frey B et al. Intensive Care Med 200;26:69-74

Incidents and Errors in Neonatal Intensive

Care

Total number of incidents included in study period

211 (45/100 neonatal admissions, 40/100 pediatric

admissions)

Frey B et al. Intensive Care Med 200;26:69-74

Incidents and Errors in Neonatal Intensive

CareIncidents by type No. (%)

Management/environment 62 (29)

Drugs 62 (29):

Wrong dose 37

Wrong drug 11

Procedures 37 (18)

Respiration 29 (14)

Equipment dysfunction 15 (7)

Nosocomial infections 6 (3)

Frey B et al. Intensive Care Med 200;26:69-74

Incidents and Errors in Neonatal Intensive

Care

Etiology

Human error (63)

Communication (14)

Organizational problems (10)

Equipment dysfunction (7)

Milieu (3)

No contributing factor identified (3)

Kugelman A et al. Pediatrics 2008;122:550-555

Iatrogenesis in Neonatal Intensive Care Units: Observational and

Interventional, Prospective, Multicenter Study

Iatrogenic Events

Cesarean delivery rates: United States, 1991-2007

Recent trends in cesarean delivery in the United States

Menacker F, Hamilton BE. NCHS data brief, no 35. Hyattsville, MD: National Center for Health Statistics. 2010

Colin, A. A. et al. Pediatrics 2010;126:115-128

RESPIRATORY MORBIDITY AND LUNG FUNCTION IN

PRETERM INFANTS OF 32 TO 36 WEEKS’ GESTATIONAL AGE

Adult Outcomes of Infants Born in Norway 1967-83 34-36 versus > 37 Weeks Gestation

Moster D, NEJM 2008;359:262

Costos del Cuidado Intensivo

Median length of hospitalization (in weeks) and med ian PMA at discharge (in weeks) according to GA at birth among 6859 VLBW infants wh o were born in NICHD NRN centers

between January 1, 2003, and December 31, 2007, and survived to discharge.

Stoll B J et al. Pediatrics 2010;126:443-456

HOSPITAL COST IN

NEWBORNS <1000g

0

20

40

60

80

100

120

0,000

100,000

200,000

300,000

400,000

<1000g 1000-2500g

HO

SP

IT

AL

CH

AR

GE

SA

LO

S (

days)

Desregionalizacion del Cuidado

Neonatal

WEEKS OF GESTATION

< 26wk 27-29 30-31

Inborn(n= 656)

Outborn(n=158)

Inborn(n=906)

Outborn(n=183)

Inborn(n=892)

Outborn(n=167)

Death 28.2 43.7* 6.9 8.2 2.9 3.0RDS 55.9 81.0* 70.0 84.5* 44.6 72.2*

≥Grade 3 IVH

16.7 37.6* 5.9 13.1* 2.9 3.9

CLD 42.3 48.4* 19.7 25.4 7.1 11.3NEC 11.4 7.5 5.5 5.5 2.1 1.9≥Stage 3 ROP

22.3 31.0 5.1 5.4 1.0 0.0

Survival without major morbidity†

32.8 18.4* 68.0 59.6* 87.8 85.0

Am J Obstet Gynecol 2003;188:617-22

Comparison of Death/Morbidity in INBORN and OUTBORN Neonates

Risk Adjusted Mortality in LBW Infants By Level of Care and NICU Size at Hospital of Birth

NICU Level and Size at Hospital Birth

BW <2000 Grams (OR [95% CI])

BW <1500 Grams (OR [95% CI])

No NICU 2.38 (1.81-3.13) 2.98 (2.10-4.24)

Intermediate NICU, any census 1.92 (1.44-2.54) 2.37 ( 1.65-3.40)

Community NICU, census <15 1.42 (1.14-1.76) 1.51 (1.1 4-2.00)

Community NICU, census ≥15 1.11 (0.87-1.43) 1.05 (0.77-1.44)

Cifuentes, J et al. Pediatrics 2002; 109: 745-751

Escasez de Personal Medico y de

Enfermeria

Escasez de Personal Medico y de Enfermeria

NEONATAL SURVIVAL

U of M - JMMC

0

10

20

30

40

50

60

70

80

90

100

777879808182838485868788899091929394959697989900010203040506070809

500-749g

750-999g

1000-1499g

<1000g

>1000g

YEARS

(%)

SU

RV

IVA

L

35th Annual International Conference

“Miami Neonatology 2011”&

Workshop: “Advances in Neonatal Respiratory Care”

Keith J. Barrington, M.D. (Montreal, Quebec)

Olaf Bodamer, M.D. PhD FACMG (Miami, FL)

Steven M. Donn, M.D. (Ann Arbor, Michigan)

Haresh Kirpalani, BM, MRCP, FRCP, MSc (Philadelphia, PA)

Helen A. Mintz-Hittner, M.D. (Houston, Texas)

Peter Rimensberger, M.D. (Geneva, Switzerland)

Barbara Schmidt, M.D. (Philadelphia, PA)

Martha C. Sola-Visner, M.D. (Boston, MA)

Win Tin, M.B.B.S. (Middleborough, United Kingdom)

Myra H. Wyckoff, M.D. (Dallas, TX )

October 26 - 29, 2011 Hotel Fontainebleau, Miami BeachGuest Speakers Topics of discussion

� New modalities of respiratory support � Volume or Pressure: Which is a better

target for neonatal ventilation?� New developments in the management

of ROP� Oxygen targets in the premature infant� Cardiovascular support in the preterm

infant� Impact of delivery room CPR on the

outcome of preterm infants� Therapies for PPHN� Blood and platelet transfusions