1. John D. Lantos M.D. Children’s Mercy Bioethics Center Children’s Mercy Hospital, KCMO What Makes the Gray Zone Gray?

2. Conventional wisdom Three ethical/medical “zones” –Non-viable: <22 (or 23) weeks –The “gray zone”: 22-26 weeks –High survival: >26 weeks Doctors determine gray zone boundaries In gray zone, parents may choose.

3. Three sources of grayness Poor chance for survival (futility) Sequelae among survivors (quality of life) Too expensive (cost-effectiveness)

4. Poor survival rates Outcomes vary from center to center. At 22 wks and 400g, survival is possible. Below 22wks and 400g, very unlikely

5. Copyright ©2004 American Academy of Pediatrics Lucey, J. F. et al. Pediatrics 2004;113:1559-1566 Peripartum outcome of inborn infants who were born at 401- 500g in Vermont-Oxford Network, 1996-2000

6. Among 400-500g infants 16% survive until discharge 35% of those admitted to the NICU survive to discharge Survival more likely after antenatal steroids and c-sections.

7. Survival by gestational age, all Canadian NICUs Data from 1996

8. 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

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

10. Algorithms improve accuracy Tyson et al – NICHD Bader et al – Israeli Neonatal Network

11. Add risk factors 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

12. 1. Gestational Age 2. Birth Weight 3. Sex 4. Singleton Birth 5. Antenatal Corticosteroids (<7 Days Before Delivery) Five factors

13. Gestational Age:23 weeks Birth Weight:450 grams Sex:Female Singleton Birth:Yes Antenatal Corticosteroids:Yes Outcomes All infants Infants given MV Survival22% 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/

14. Gestational Age:25 weeks Birth Weight:575 grams Sex:Male Singleton Birth:No Antenatal Corticosteroids:Yes All infants Infants given MV Survival53%54% Survival Without Profound Impairment 34%35% Survival Without Moderate to Severe Impairment 17%18%

15. Birthweight percentiles Bader et al Peds 2010

16. Mortality rates by GA and birthweight percentile Bader et al Peds 2010

17. Physical and cognitive impairments Quality of life is complicated –Probability of a bad outcome, –Judgment about how bad. Probabilities are fraught with uncertainty Judgments are fraught with subjectivity

18. Key question How bad does life have to be before it is thought to be worse than death?

19. 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

20. 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.

21. 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.

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

23. 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

24. “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.

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

26. Summary of empirical studies Parents more tolerant of disabilities than doctors or nurses They rate quality of life higher More likely to opt for treatment even if survival is likely to be with neurocognitive problems. Parents who have had a preemie are more likely to favor treatment.

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

28. 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.”

29. Cognitive Scores for 241 Extremely Preterm Children and 160 Age-Matched Classmates Who Were Full Term at Birth, According to Sex and Completed Weeks of Gestation. Kaufman Assessment Battery for Children scores for the Mental Processing Composite or developmental scores according to the Griffiths Scales of Mental Development and NEPSY (possible range, 39 -150) Marlow et al. NEJM, 2005: 352 (1): 9

30. Disability and cost-effectiveness Studies of the burden of disability also incorporate cost-effectiveness analyses. Outcomes reported as –$$/QALY (quality-adjusted life-year) or –$$/DALY (disability-adjusted life-year)

31. Cost-effectiveness What is the cost of saving a life? What is the long term cost of health needs and educational needs? How do the costs of saving a premature baby compare to other medical costs?

32. Copyright ©2004 American Academy of Pediatrics Doyle, L. W. et al. Pediatrics 2004;113:510-514 Cost-effectiveness and cost-utility ratios (1997 Australian dollars)

33. Cost-benefit analysis, premature babies, 1960 and 1990 Cuttler and Meara

35. Summary To define the gray zone, need to consider survival, impairment, and cost. Only survival differs significantly by gestational age or BW/GA – cost and QOL do not. How likely does survival need to be in order to deem treatment obligatory?

36. Ethics and knowledge Precise, individualized predictions of survival could eliminate the gray zone: –Treat babies who will survive –Do not treat babies who will die Precise, individualized predictions of impairment will not…. –Trisomy 13 and 18

37. Starting and stopping Many ethical frameworks focus on the decision about starting treatment Preferable to focus on decisions about when to stop. Parental demands for futile treatment far more common than parental refusals of beneficial treatment.

38. Key question Can we tolerate moral diversity?