1. Babies in the gray zone Who should decide? And on what basis? John D. Lantos M.D. Director, Children’s Mercy Bioethics Center Children’s Mercy Hospital, KC Professor of Pediatrics, UMKC

2. Disclosures No conflicts of interest

3. One thing we know for sure: Treatment of ELGANs varies widely between centers.

4. Resuscitation and survival at various gestational ages - PSVMC Gestational age% Vent% survival 22 weeks: 0%0 23 weeks: 39% 0 24 weeks: 62% 38 25 weeks: 83% 74 26 weeks: 100% 98 Kaempf, J. W. et al. Pediatrics 2009;123:1509-1515

5. Copyright ©2004 American Academy of Pediatrics Hoekstra, R. E. et al. Pediatrics 2004;113:e1-e6 Survival by GA between 1986 and 2000, University of Minnesota

6. Survival by GA, NICHD neonatal network, 2008 22 weeks – 5% 23 weeks - 26% 24 weeks - 56% 25 weeks - 76% www.nichd.nih.gov/neonatalestimates Tyson, et al,NEJM, 2008

7. Reported survival rates - 23 weeks Portland St. Vincent – 0% survival University of Minnesota – 66% NICHD – 26%

8. International differences are even more striking

9. Copyright ©2008 American Academy of Pediatrics Zeitlin, J. et al. Pediatrics 2008;121:e936-e944 Survival rates at 11 European centers, EGA 24-27 weeks, 2003

10. Canadian data, 11 centers, 1996 Lee SK et al, Pediatrics 11/ 2000, 1070-1079

11. Copyright ©2006 American Academy of Pediatrics Kusuda, S. et al. Pediatrics 2006;118:e1130-e1138 GA-specific neonatal mortality, Japan, 2003 From 42 centers in Japan, 2003

12. International differences in survival for babies at 24 weeks EGA Europe – 5-10%* Canada – 50% Minnesota – 81% Japan – 75% NICHD - 56% *Netherlands has 0% survival

13. Substantive and procedural criteria Substantive – when is it permissible to withhold or withdraw treatment? –What are the boundaries of the gray zone? –Do they shift over time? Procedural – in the gray zone, whose views prevail? –Doctors? –Parents? –Society?

14. Conventional wisdom Three ethical/medical “zones” –Non-viable: <22 (or 23) weeks –The “grey zone”: 22-26 weeks –High survival: >26 weeks Doctors determine grey zone boundaries In the grey zone  treatment is optional Thus, for babies in the grey zone, parents should be given choices.

15. Official statements “Decisions about non-initiation or withdrawal of intensive care should be made by the health care team and the parents of a high- risk infant working together.” “Parents should be active participants in the decision making process.” American Academy of Pediatrics, Committee on Fetus and Newborn, Bell EF, Pediatrics, 2007

16. Parent groups agree In medical situations involving very high mortality and morbidity, great suffering, and/or significant medical controversy, fully informed parents should have the right to make decisions regarding aggressive treatment for their infants. –Harrison H. Pediatrics, 1992.

17. Who actually makes decisions? Survey Every practicing neo in New England –to what extent is decision-making shared between neonatologists and parents? –what role do neonatologists see themselves as playing in these conversations? »Bastek et al, Pediatrics, Aug, 2005

18. Who Makes the Final Decision Regarding Resuscitation in the Delivery Room? Doctors views TotalNeoParents Neo and ParentsOB In your opinion, who should make the final decision to withhold resuscitation in the delivery room? 14919 (13)16 (11)114 (77)0 (0) In your opinion, who does make the final decision to withhold resuscitation in the delivery room? 14674 (50)13 (9)59 (40)0 (0) Bastek et al, Peds, August 2005

19. Who Makes the Final Decision Regarding Resuscitation in the Delivery Room? Doctors views TotalNeoParents Neo and ParentsOB In your opinion, who should make the final decision to withhold resuscitation in the delivery room? 14919 (13)16 (11)114 (77)0 (0) In your opinion, who does make the final decision to withhold resuscitation in the delivery room? 14674 (50)13 (9)59 (40)0 (0) Bastek et al, Peds, August 2005

20. What would you do? 1996 and 2003. 500 U.S. neonatologists 4 potential scenarios: –(1) BW <500g, GA <23 weeks, –(2) BW of 500-600g, GA 24 weeks, –(3) BW of 601 - 750 g and GA 25 weeks, –(4) BW of >750 g and GA 26 weeks. Choices –(1) full resuscitation, –(2) comfort care, or –(3) deferral to the parents' wishes. Singh et al, Pediatrics, Sept, 2007

21. Copyright ©2007 American Academy of Pediatrics Singh, J. et al. Pediatrics 2007;120:519-526 Delivery room responses as a function of GA

22. Surveys Most of the time, pediatricians/neonatologists make the resuscitation decisions themselves. Why? Parents’ decisions seem too uninformed and idiosyncratic.

23. “The fact that an abnormal baby was born to me and my wife was a simple accident. Neither of us is responsible. All I can do is leave him at a university hospital and make certain that he’ll weaken and die naturally.” Some parents don’t want life- saving treatment for their babies

24. Some want more treatment than doctors think is appropriate “Before Annie was diagnosed, we had never heard of Trisomy 13. Once her chromosomes came back, the doctors discussed with us the possibility of terminating the pregnancy. We chose not to terminate. Instead, we decided that we would treasure the time that we had with her.” Farlow B, Misgivings, Hastings Ctr Report, 2010

25. “Annie developed acute respiratory distress. She was admitted to the PICU. The intensivist seemed annoyed that we would not agree to a DNR order. We (later) learned that a DNR order had been entered without our knowledge or consent.” Farlow, Hastings Ctr Report, 2010

26. Some parents initially don’t want treatment, but then change their minds.

27. This Lovely Life Mother: “We want the twins to be DNR. I was against resuscitation at birth and I’m not in favor of prolonging life support. These babies were born too early.” Doctor: “It is not typical for us to include this type of order in the chart.”

28. The day before, I stood outside of the NICU and cried and threatened to rip out every tube and line attached to my twins. But something had changed in the last 24 hours, something I wished I could explain to my father…While I was only three days into this ordeal, I had come to accept these compromised babies as mine.”

29. “My milk had come in. I needed to decide if I would pump my milk or not, if there was a purpose to that act of motherhood. Everything was happening in the now and there was no standing back. I wished I could find words to describe how this whole mess felt oddly fated, that I was somehow meant to be Evan and Ellie’s mother.”

30. Some parents just don’t want to be involved in decisions “In 2005, our daughter Violette was born at 24 weeks and 5 days. Violette had a stormy course. When she was sickest, so was I. I was better able to cope as she gradually became more stable; by the time she was on continuous positive airway pressure, I was fine.” Janvier A, Arch Pediatr Adolesc Med. 2007;161(9):827.

31. I’m only punching in “I loathed visiting the NICU while she was unstable. I hated being encouraged to participate in her care. I visited because I felt I had to show the nurses and social workers that I was a normal parent who was bonding. I "had to" do kangaroo care and hold my 700-g baby as she became dusky.” Janvier A, Arch Pediatr Adolesc Med. 2007;161(9):827.

32. I’m only punching in I held Violette and told nurses that I wanted to, even if I dreamt every night of dropping her and seeing her eyes roll on the floor and her brain gushing out. Janvier A, Arch Pediatr Adolesc Med. 2007;161(9):827.

33. “Our wishes, judgments, and thoughts were rarely of interest to the medical staff, who arrogated decisions to themselves as though we did not exist.” Some parents feel ignored

34. . “Pessimistic assessments of Andrew’s condition and prognosis had been made by the Neurology Department, though they were never mentioned to us by anyone.”

35. “The NICU staff members went out of their way to hide information from us about the likelihood that David would have neurologic damage. We weren’t given guidance about, for example, what a grade III brain bleed was. They said, ‘He may be a little behind.’” Gary Horn, about his son David, born at 24 weeks in 1993, quoted in Baby at Risk, 2007.

36. “If doctors and nurses knew what our life was going to be like, why shouldn’t we have known? They need to be more honest with parents.” –Debby Barrett, mother of Michael, born at 1 lb, 15 oz and 24 5/7 weeks, quoted in Baby at Risk, 2007.

37. Key question: Generally speaking, what do parents want?

38. Parent and professional agreement with the statement: “I believe an attempt should be made to save all infants regardless of birth weight.” Most say they want “everything.” Streiner et al Peds, 2001

39. Parent and professional agreement with the statement: “I believe an attempt should be made to save all infants regardless of birth weight.” But many do not…. Streiner et al Peds, 2001

40. Copyright ©2009 American Academy of Pediatrics Lam, H. S. et al. Pediatrics 2009;123:1501-1508 More likely than health care workers to want to save babies “at all costs.”

41. Copyright ©2009 American Academy of Pediatrics Lam, H. S. et al. Pediatrics 2009;123:1501-1508 But many disagree… Only about 50%

42. Can consistent counseling convince parents not to treat babies in grey zone? Counseling Pregnant Women Who May Deliver Extremely Premature Infants –Retrospective chart review –All women threatening premature birth at 22-26 weeks at one hospital in Oregon, 6/03-12/06 –Comprehensive counseling by ob and neo »Kaempf et al Peds, June, 2009

43. Copyright ©2009 American Academy of Pediatrics Kaempf, J. W. et al. Pediatrics 2009;123:1509-1515 PSVMC continuum approach to periviability counseling

44. “We do not recommend NICU care for infants born at <25 weeks: (1) the chance of NICU death or significant neurologic injury is generally 50% or more, (2) our providers believe it neither reasonable nor fair to insist on resuscitation of infants who may have enormous long-term health issues that we may not help the family cope with or resolve.”

45. Initial Neonatal Care Preferences After Counseling Weeks at Birth (PMA)n Resuscitate, n (%) Comfort Care, n (%) No Decision, n (%) 22/0 – 22/6 182 (11)12 (67)4 (22) 23/0 – 23/6 549 (17)35 (65)10 (19) 24/0 – 24/6 7533 (44)24 (32)18 (24) 25/0 – 25/6 7855 (71)7 (9)16 (20) 26/0 – 26/6 3526 (74)2 (6)7 (20)

46. Preferences before delivery – many choose comfort care or are unsure. Weeks at Birth (PMA)n Resuscitate, n (%) Comfort Care, n (%) No Decision, n (%) 22/0 – 22/6 182 (11)12 (67)4 (22) 23/0 – 23/6 549 (17)35 (65)10 (19) 24/0 – 24/6 7533 (44)24 (32)18 (24) 25/0 – 25/6 7855 (71)7 (9)16 (20) 26/0 – 26/6 3526 (74)2 (6)7 (20)

47. Under 25 weeks, <50% wanted resuscitation Weeks at Birth (PMA)n Resuscitate, n (%) Comfort Care, n (%) No Decision, n (%) 22/0 – 22/6 182 (11)12 (67)4 (22) 23/0 – 23/6 549 (17)35 (65)10 (19) 24/0 – 24/6 7533 (44)24 (32)18 (24) 25/0 – 25/6 7855 (71)7 (9)16 (20) 26/0 – 26/6 3526 (74)2 (6)7 (20)

48. Final decisions regarding resuscitation – a shift toward more aggressive care…. Weeks at Birth (PMA)n NICU Resuscitatio n, n (%) Palliative Comfort Care, n (%) Time to Death Comfort Care, Range, min NICU Death, n (%) a Overall Survival % 22 130 (0)13 (100)5–138—0 23 187 (39)11 (61)5–1717 (39)0 24 15 (62)9 (38)10–1246 (25)38 25 2319 (83)4 (17)34–1192 (9)74 264343 (100)0 (0)—1 (2)98 - Kaempff et al Peds, June 2009

49. Shift from initial parental preference to ultimate treatment decision 22 weeks: 11%  0% wanted resuscitation 23 weeks: 17%  39% 24 weeks: 44%  62% 25 weeks: 71%  83% 26 weeks: 74%  100% From 23 weeks onward, parents predictably shifted from theoretical choice of non-treatment to actual choice of treatment – in spite of doctors’ advice about 23 and 24 weeks.

50. Why do many parents want more treatment than doctors recommend? They don’t understand how bad the baby’s life will be? They do understand the facts, but disagree about values?

51. Misunderstanding or value clash? 587 subjects, 4/05-7/07, Hong Kong. –135 health care workers, –155 mothers of term infants, –288 parents of preterm infants. Ranked five health states and death »Lam et al, Pediatrics, June, 2009

52. Worst health states 1. Death. 2. Severe global impairment – wheelchair, intelligence of 1y.o., unable to speak, read or write, incontinent, no independent ADLs. 5. Moderate global impairment – crutches, attends special school, cannot read or write, unable to live independently, continent.

53. Copyright ©2009 American Academy of Pediatrics Lam, H. S. et al. Pediatrics 2009;123:1501-1508 Bars represent 3 different groups of respondents. Blue stripe: proportion who thought that death was worst outcome, severe delay next, and moderate delay best. Red stripe: those who thought severe delay was worst outcome, followed by death and then moderate delay.

54. What percentage think that severe disability is worse than death? Doctors and nurses - 55% Mothers of term babies – 40% Parents of preemies – 25%

55. Parents and professionals ratings of quality of life Interviews with: –100 neonatologists –103 neonatal nurses from 3 NICUs –264 adolescents, including 140 who were ELBW infants and 124 sociodemographically matched term controls –275 parents of the recruited adolescents. Main Outcome Measure Preferences (utilities) for 4 to 5 hypothetical health states of children. –Saigal et al JAMA 1999

56. “Best” and “Worst” children Jamie – can see, hear, talk, walk, bend, lift, jump, and run normally, does schoolwork more slowly than classmates. Pat – blind, deaf, unable to talk, needs equipment to walk, learns schoolwork very slowly and needs special help, needs help from another person to eat, bathe, dress or use the toilet.

57. Saigal, S. et al. JAMA 1999;281:1991-1997. Comparison of Preferences of Health Care Professionals and Parents for 4 Hypothetical Health States

58. Studies suggest that…. Parents are more tolerant of disabilities than doctors or nurses In the most impaired babies, they rate quality of life higher More likely to opt for continued treatment even facing neuro-cognitive problems. Parents who have had preemies feel even more strongly than parents who haven’t.

59. Can better data about outcomes help? Neonatologists have worked hard to refine prognostication. Prognostication is now epidemiologically precise but individually uncertain. Information is ambiguous “Honesty” requires judgment calls.

60. NICHD neonatal estimator A simple Web-based tool allows clinicians to estimate the likelihood that intensive care will benefit individual infants. www.nichd.nih.gov/neonatalestimates Tyson, et al, NEJM, 2008

61. Five factors Gestational Age Birth Weight Sex Singleton Birth Antenatal Corticosteroids (<7 Days Before Delivery)

62. Gestational Age:23 weeks Birth Weight:450 grams Sex:Female Singleton Birth:Yes Antenatal Corticosteroids:Yes Outcomes Outcomes for Outcomes for All Infants Infants with MV Survival 22% 32% Survival Without Profound Impairment 14% 21% Survival Without Moderate to Severe Impairment 8% 12% http://www.nichd.nih.gov/about/org/cdbpm/pp/prog_epbo/

63. Gestational Age:25 weeks Birth Weight:575 grams Sex:Male Singleton Birth:No Antenatal Corticosteroids:Yes All infants Infants given MV Survival 53%54% Survival Without Profound Impairment 34%35% Survival Without Moderate to Severe Impairment 17%18%

64. Data can be presented in different ways: How many 500g singletons survive unimpaired? 23 week boys 16% 24 week boys 24% 25 week boys 33% 25 week girls 47% If “grey zone” means >50% survival without impairment, all are in the “gray zone.”

65. Among 500g singletons, how many survivors are unimpaired? Of all babies Survivors only 23 week boys 16%57% 24 week boys 24%61% 25 week boys 33%64% 25 week girls 47%76% If “grey zone” means <50% survival without impairment, none are in the “gray zone.”

66. Copyright ©2007 American Academy of Pediatrics Wilson-Costello, D. et al. Pediatrics 2007;119:37-45 How many babies do well? If “do well” means “survive without impairments” 40% 50% 32%

67. Copyright ©2007 American Academy of Pediatrics Wilson-Costello, D. et al. Pediatrics 2007;119:37-45 How many babies do well? 40% 50% 32% 72% 66% 76%

68. How many are “intact?” 50% of all babies survive unimpaired 76% of all survivors are unimpaired Improvement in overall unimpaired survival. 32%  40%  50% No trend in percent of survivors who are unimpaired. 72%  65%  75%.

69. In the grey zone, do the tinier babies do predictably worse? Answer is not so clear

70. Med 2000;343:378-384 Overall Disability at 30 Months for 314 Children Born at 22 through 25 Weeks of Gestation Weeks of Gestation Wood, et al, NEJM, August 2000

71. Disability rates among survivors, by gestational age 22 weeks - 1/2 (50%) 23 weeks - 14/26 (54%) 24 weeks - 52/100 (52%) 25 weeks - 84/186 (45%) In each group, half of disability was “severe.”

72. Differences in Disability Rates at 30 months of age Gestational age (wks)<232425 --------------------------------------------------------------------------------- Bayley scores mental 848584 psychomotor858787 No developmental disability423039 Severe disability 271917 No neuromotor disability857476 No sensory disability586469

73. Other predictors may be more powerful than gestational age Girls do better than boys Blacks do better than whites Outcome is better for babies in high SES families compared to low. At any gestational age, bigger babies do better than smaller babies.

74. Key question Which is the worst outcome? – Death or severe impairment – Severe impairment only Which is the “best” death –Comfort care only if intact survival is unlikely –Treatment withdrawal only after a trial of therapy?

75. Who should decide? Doctors want evidence-based solutions to reduce the variation and uncertainty. For parents, statistical evidence doesn’t matter so much. For them, each baby is a unique case.

76. Doctors are all alike, parents are all different Doctors want formulae. Parents want individualized decisions.

77. What to do? Data define the parameters of freedom. Communication shapes choices within those parameters. Statistics help, but only a little. Scientific certainty only leads to humanistic challenges.

78. Limitations of prognostic data What if we could predict with 100% certainty that a baby would either die or be severely impaired? Many parents would probably still choose active intervention. –See, e.g. the curious debate about trisomy 13/18.

79. Thanks

80. Copyright restrictions may apply. Robertson, C. M. T. et al. JAMA 2007;297:2733-2740. Number of Children With Cerebral Palsy Per 1000 Gestational Age-Specific Live Births of 20 Through 25 Weeks and 26 Through 27 Weeks and With Birth Weights Between 500 and 1249 g in Relation to 10 Birth-Year Groups Over 30 Years

81. Vincer et al, Peds, 2006

82. Himmelman et al, Acta Paediatrica 2005

83. CP rates over last fifty years – US, Europe, Australia Based on 50 reports of CP prevalence rates published in the last twenty years Paneth et al Clinics Perinatol 2006

84. CP rates over last fifty years – US, Europe, Australia Babies <1500g Based on 50 reports of CP prevalence rates published in the last twenty years Paneth et al, Clinics Perinatol 2006