1. Outcomes of Extremely Preterm Infants
2016 Developmental Care Conference
12/6/16
Outcomes of Extremely Preterm Infants
Ravi Mangal Patel, MD MSc
Assistant Professor of Pediatrics
Division of Neonatology, Emory University and Children’s Healthcare of Atlanta
@ravimpatelmd

2. Disclosures
I have no relevant conflicts of interest to disclose

4. Learning objectives At the end of this talk, you should know:
Recent data on survival for extremely preterm infants
The spectrum of neurodevelopmental outcomes among surviving extremely preterm infants

5. Survival improving for Extremely preterm infants

6. *
Patel RM, et al. N Engl J Med. 2015
*P=0.003

7. Survival for extremely preterm infants
Patel RM, et al. N Engl J Med. 2015

8. Changes in survival over time in US
Data from NICHD Neonatal Research Network

9. Survival of extremely preterm infants in high-income countries

10. Importance of denominators in understanding birth outcomes
Stillbirth
Patient
admitted
at 22wk
gestation
Comfort care
Delivery room
death
Live-birth
Resuscitation
(active treatment)
Death in
hospital
Survival to NICU
admission
Survival to
hospital discharge

11. Importance of denominators in understanding birth outcomes
Stillbirth
Patient
admitted
at 22wk
gestation
Comfort care
Delivery room
death
Live-birth
Resuscitation
(active treatment)
Death in
hospital
Survival to NICU
admission
Survival to
hospital discharge

12. Importance of denominators in understanding birth outcomes
Stillbirth
Patient
admitted
at 22wk
gestation
Comfort care
Delivery room
death
Live-birth
Resuscitation
(active treatment)
Death in
hospital
Survival to NICU
admission
Survival to
hospital discharge

13. Importance of denominators in understanding birth outcomes
Stillbirth
Patient
admitted
at 22wk
gestation
Comfort care
Delivery room
death
Live-birth
Resuscitation
(active treatment)
Death in
hospital
Survival to NICU
admission
Survival to
hospital discharge

14. Birth outcomes in population-based cohorts
Adapted from
Costeloe KL, et al. BMJ 2012

15. Birth outcomes in population-based cohorts
Unpublished data

16. Birth outcomes in population-based cohorts
22wk: stillbirths 85%
23wk: stillbirths 75%
22wk: stillbirths 45%
23wk: stillbirths 19%
22wk: stillbirths 65%
23wk: stillbirths 45%
Unpublished data

17. Birth outcomes in population-based cohorts
Unpublished data

18. Survival after admission to the NICU
Single center in Germany (n=106)
81% received active care
Mehler K et al. JAMA Pediatrics 2016

19. Effect of resuscitation
(active treatment)
on survival

21. Modes of active treatment
Rysavy MA et al. N Engl J Med 2015

22. Active treatment by gestational age
Figure 1. Rates of Active Treatment by Gestational Age at Birth. Point values represent the mean percentage, across all hospitals, of infants born at a given gestational age (in weeks and days) who received active treatment. Vertical bars represent 95% confidence intervals. Blue dashed lines indicate the mean rate of active treatment among infants born during a given week of gestation, and blue dotted lines indicate 95% confidence intervals.
Rysavy MA et al. N Engl J Med 2015

23. Rates of active treatment by hospital
Rysavy MA et al. N Engl J Med 2015

24. Effect of active treatment at 22wk
Rysavy MA et al. N Engl J Med 2015

25. Change in survival with active treatment
Whisker bars: 95% CI
Rysavy MA et al. N Engl J Med 2015

26. Change in survival estimates after birth by postnatal age
Study in 362 NICUs in the US from 1997 to 2013 among
64,896 infants born at 22 to 29 weeks’ gestational age.
Overall survival increased from 80% in 1997 to 88% in 2013
Hornick CP et al. Early Hum Dev 2016

27. Point prevalence of survival by age
Hornick CP et al. Early Hum Dev 2016

28. How do we define disability?
Long-term outcomes:
How do we define disability?

29. Definitions of neurodevelopmental disability (or impairment or delay)
Cognitive impairment (mental retardation)
Evaluated using Bayley Scales of Infant and Toddler Development (BSID)
Motor impairment (cerebral palsy)
Evaluated using BSID and Gross Motor Function Classification Scale (GMFCS)
Deafness
Blindness

30. BSID used to define cognitive impairment

31. BSID used to define impairment based on population norms
1 SD below mean
(Bayley Scales of Infant and Toddler Development)

32. BSID used to define impairment based on population norms
2 SD below mean
(Bayley Scales of Infant and Toddler Development)

33. GMFCS used to determine severity of motor impairment

34. Long-term outcomes in extremely preterm infants
Patel RM. Am J Perinatol 2016

35. Prevalence of mild or no disability
Patel RM. Am J Perinatol 2016

36. Prevalence of moderate disability
Patel RM. Am J Perinatol 2016

37. Prevalence of severe disability
Patel RM. Am J Perinatol 2016

38. Factors beyond gestational age
Tyson JE, et al. NEJM 2008

39. neurodevelopmental outcomes, with dynamic changes in early childhood
Wide spectrum of
neurodevelopmental outcomes,
with dynamic
changes in early childhood

40. Disability for extremely premature infants at 6 years of age (EPICure)
Severe Disability 22%
Versus 0% in classmate controls
Moderate Disability 24%
Versus 1% in classmate controls
Mild Disability 34%
Versus 18% in classmate controls
No Disability 20%
(CP, blindness, deafness, IQ <3SD below mean) We identified all extremely preterm children (gestation
at birth, no more than 25 weeks and 6 days)who were born in the United Kingdom and Ireland
between March and December (82 percent) participatedin this study at a median age of six years and
four months (range, five years and two months to seven years and three months).
Marlow N, et al. N Engl J Med 2005

41. Cognitive scores for extremely preterm infants at 6 years of age (EPICure)
Marlow N, et al. N Engl J Med 2005

42. Cognitive scores for extremely preterm infants at 6 years of age (EPICure)
IQ +/- 1 SD
from mean
Marlow N, et al. N Engl J Med 2005

43. Cognitive gain over time
Gain of 20 points in cognitive score
A child scoring 68 at 18 mo
could score 88 at 5yr
Schmidt B et al. JAMA 2012

44. Social variables influence cognitive gains between 18 mo and 5 years
Social advantages:
-Maternal college education
-Paternal college education
-Employed caregiver
Manley BJ et al. J Pediatr 2015

45. Spectrum of long-term outcomes among survivors
Disability at mo corrected age:
Data from Rysavy et al. NEJM 2015

46. What about more mature preterm infants
Bentley JP et al. Pediatrics 2016

47. How do extremely preterm infants do in adulthood ?

48. Outcomes compared to normal birth weight infants.
Researchers evaluated 100 of 165 very-low birth weight survivors in Ontario, CA who were aged 29 to 36 years.
Outcomes compared to normal birth weight infants.
Saigal S et al. JAMA Pediatrics 2016

49. Saigal S et al. JAMA Pediatrics 2016

50. Saigal S et al. JAMA Pediatrics 2016

51. Saigal S et al. JAMA Pediatrics 2016

52. Tools for counseling

53. NICHD NRN Outcomes Calculator

57. NRN outcome estimator limitations
Data do not reflect changes in outcomes over last 15 years
Misclassification rate of ~25%
Center is not included as a factor
Imprecision in outcome estimate not quantified

58. Other decision aid tools
Úrsula Guillén, et al. J Pediatr 2012

60. Summary
Survival among periviable infants at weeks’ gestation has improved in recent years
Death more common outcome at 22 to 23 weeks
Substantial center variation in outcomes, largely because of variation in active treatment (resuscitation)
Neurodevelopmental outcomes are difficult to predict and can change over time
Limitations in tools for prediction of outcomes should be considered if using to counsel patients

61. Thank you.
@ravimpatelmd