Professor Tom Clarke, Rotunda Hospital & Royal College of Surgeons in Ireland 6 th Pan Arab Neonatology Forum, Am

1. Outcome and Ethical Decisions in Infants Born at the Threshold of Viability Professor Tom Clarke, Rotunda Hospital & Royal College of Surgeons in Ireland 6th Pan Arab Neonatology Forum, Amman, 2009

2. Issues surrounding the care of infants born at the limits of viability • Historical perspective • Ethics • Outcome • Epicure study • Other Studies • What to do?

3. History Increased Survival with Disability Reported in Past 30 to 40 Years “Not strive officiously" (Lancet editorial, 1970) “The morality of drastic intervention" (GB Avery, Neonatology, textbook, 1981) “Which infants should not receive intensive care" (Campbell, Arch Dis Child 1982) “Death as an option in neonatal care?" (Whitelaw, Lancet 1986)

4. Ethics Ethics Relating to morals Moral Concerned with goodness or badness The distinction between right and wrong

5. Ethics: major principles • Autonomy • Beneficience • Non-maleficience • Justice • Truthfully • Fairly • Competence • Confidentiality • Conflicts of interest • Paternalism • Allocation limited health care resources Principle is a comprehensive & fundamental law, doctrine or assumption

6. Three parties concerned in neonatal period • The infant • The doctor and other carers • Society in general, particularly parents, relatives, friends

7. Three groups of infants • Infants born at the limits of viability • WHO ‘threshold of viability’ infants between 22 and 28 weeks gestation • Infants with significant brain damage • Normal life extremely unlikely • Infants with complex & often multiple congenital abnormalities • Generally affecting brain & spinal cord

8. Different ethical views All possible efforts should be made to preserve life for every infant Where high likelihood of severe handicap, no medical treatment should be given other than to relieve suffering (comfort care & allow to die) Some (minority) consider that letting infant die is not morally different to actively intervening NEITHER MEDICAL SCIENCE , ESTABLISHED CUSTOMS OR THE LAW PROVIDE ALL THE ANSWERS

9. Who decides? Parents & physicians almost always think of child’s best interests Questions raised Can they, individually or together, always make decisions in the infant’s best interests?

10. Potential conflicts • Parents • Concerns about effect on the family, financial realities & future • Physicians • May personalise situation, e.g emphasis on intellectual outcome • Interest in new medical treatments • Enhancing survival statistics (avoiding complicated patient with poor prognosis) • Bioethical Review Committees in many countries

11. Canadian Paediatric Society • Criteria proposed which forbid hastening death but consider withholding care if: • There is irreversible progression of disease • Treatment will be ineffective and harmful • Life will be short with treatment & non-treatment will permit greater comfort and caring • Future will entail intolerable pain and suffering American Medical Association 2002. Code of Medical Ethics. (similar)

12. General principles of withholding care • Multidisciplinary approach encouraged • Involve nurses, doctors & other professional staff • Involve parents in decision making process • Attempt to reach consensus • Decisions made in best interests of most vulnerable, the infant

13. Outcome Morbidity & mortality at limits of viability

14. Measurements of Severe Disability • Requires ongoing support • Oxygen or ventilator support • Special provision for feeding • Responds only to light or is blind • Requires hearing aids • Significant developmental delay • Overall developmental level of one year or less at age two years • Unable to sit unsupported • Unable to use hands for feeding

15. Predictors of significant disability or handicap Difficult to accurately predict likelihood of disability • Infants at highest risk • Extreme prematurity (especially infants born at 23 to 24 weeks gestation) • Infants who were critically ill or remained ill for long periods (several weeks) • Infants with identifiable brain abnormalities • Occuring before birth or in neonatal period • Detected by cranial ultrasound or MRI

16. EPICure Study of all children born in 1995 at 25 completed weeks gestation or less in UK and Ireland • Initial survival rates over first 7 days: • At 25 weeks: 75% • At 24 weeks: 60% • < 24 weeks: 45%

17. EPICure study: at term equivalent Of the 314 infants discharged home 62% had one or more of following problems at full term equivalent

18. EPICure study at 1 year • There were continuing medical problems for 31% of the children

19. EPICure study: outcomes at 6 years Marlow et al. N Engl J Med 2005; 352:9-19 12% (30 children) had disabling cerebral palsy

20. Epicure: neurodevelopmental outcomes • Rates of severe disability* at 6 years consistent with earlier assessments • 86% of infants diagnosed with severe disability at 30 months remained moderately or severely disabled at 6 years • However rates of moderate and mild disabilities at 6 years of age were higher & poorly predicted by findings at 30 months • While 80% of survivors had some form of disability at 6 years, 34% of these were mild such as mild hearing impairment, squint or refractive error * (Severe disability = Cerebral palsy, blindness, severe deafness, or IQ < 55)

21. Gestation at Birth 23 weeks or less 24 weeks 25 weeks No Disability 12% 14% 24% Mild Disability low normal IQ scores, wears glasses & has a squint, mild hearing loss, minor neurological abnormalities 25% 36% 35% Moderate Disability moderate learning problems, cerebral palsy but walking, hearing aids, some vision deficit 38% 22% 22% Severe Disability severe learning problems, cerebral palsy & not walking, profound deafness, blindness 25% 29% 18% EPICure Results: Percentage of Children with different degrees of disability http://www.nottingham.ac.uk/human-development/Epicure/Interpretation/Page10d.htm

22. Outcome in Minneapolis tertiary referral centre by gestational age at mean follow-up of 47.5 months(1986 -2000)(Hoekstra, R. E. et al. Pediatrics 2004;113:e1-e6.) Survival at 23 weeks often has bad outcome

23. Childhood Impairment • Recommended that developmental needs in children be assessed in terms of; • Impairment of function • Activity limitations • Participation in community life Simmeonson et al. Disability Rehabilitation 2003 • Developmental tests not a measure of resiliency • Ability to adjust to change or misfortune

24. Neonatal Research NetworkTyson J E, Parikh, NA et al. N Engl J Med 2008 • NICHHD study (19 hospitals) 1998 to 2003 • 4,446 infants born at 22 to 25 completed weeks • 83% intensive care (mechanical ventilation) • Outcomes at 18 to 22 months corrected age (94% follow up) • 49% died • 61% died or profound impairment • 73% died or impairment

25. Neonatal Research Network; moving beyond gestational ageTyson J E, Parikh, NA et al.. N Engl J Med 2008 • Infants who received intensive care; Other factors, besides gestational age, are associated with risk of death and neuro-developmental impairment • Antenatal steroids • Female sex • Singleton birth • Higher birth weight (per 100 gram increment) • These factors are associated with risk reductions similar to a one week increase in gestational age

26. Academic achievements & educational needs: EPICure study Johnson et al . Arch Dis Child, Foetal Neonatal Ed 2009 • 219 of 307 surviving infants at age11 years • 13% attended special schools • 87% attended mainstream education • Teachers rated 50% below average range (compared with 5% of classmates) • 57% required special education (OR 10, CI 6 – 18) • Special education needs expected to increase as children enter secondary school

27. Cognitive outcome in school-age children (1996–2002) Davis DW. Neonatal Network 2003 • High proportion of ELBW children • Function within the normal range on (IQ) tests • But exhibit wide variety of more subtle motor and behavioural problems • Approximately half of ELBW children require additional educational services

28. Outcomes for the extremely premature infant. (2004 – 2007)Robertson et al, Pediatric Neurology 2009 • “More recent reports herald a more positive perspective on the outcome for extremely premature survivors” • Childhood CP rates as low as 19% • Vision & hearing loss less than 1% • Rate overall intellectual impairment not improved • Reduced rates of impairment increasingly reported

29. Improved Neurodevelopmental Outcomes for ELBW Infants 2000-2002Wilson-Costello D et al, Pediatrics, 2007 • Compared ELBW outcomes 1982-89, 1990-99 and 2000-2002 • Cerebral palsy decreased 13% to 5% • Neurodevelopmental impairment decreased 35% to 23%

30. The law & extreme prematurity in western countries • Canada • Very limited common law specifically relating to extremely premature infants • Australia • Once a baby is born alive it is recognised as a legal person • Authorises medical treatment for an infant even if against the wishes of parents • Parents do not have absolute right to decide treatment for an infant • Japan • Extremely premature infant protected by Japanese Eugenic Protection Act • Defines the foetal viability limit as ‘the minimal duration which renders foetuses capable of extra uterine life’ (22 weeks)

31. Comparison Management Strategies in New Jersey & the Netherlands. 1984 -1987 Lorenz JM, Paneth N et al. Pediatrics 2001;108:1269-74 • Near universal provision of intensive care (N. J.) compared with selective initiation at 25 weeks or less • 24.1 additional survivors per 100 live births • 7.2 additional cases of cerebral palsy • Cost of 1372 additional ventilator days per 100 live births Probably near extreme end of a range of approaches but both would be considered valid

32. Making decisions • Guidelines regarding whether to administer intensive care to EP infants are controversial • More common -increasing numbers of EP births • Advanced maternal age • Increased use of assisted reproductive technology • Publicity about "miracle babies" in media • Intensive care is provided selectively on the basis of specific gestational- age thresholds

33. Nuffield Council on Bioethics, November 2006.Critical Care Decisions in Fetal and Neonatal Medicine; Ethical Issues • Recognise nature & complexities decision making in critical care • Regard moment of birth as significant moral and legal point of transition for judgements about preserving life • Some circumstances no obligation to preserve life • Resources - Do the best possible for “the patient in front of them” • Code of practice should be developed • Best interests of child • More transparent criteria • Palliative care

34. Nuffield Council of Bioethics – guidance • 21weeks No resuscitation. (experimental research protocol only) • 22 weeks No resuscitation, unless at parents request if they have been fully informed of risks and likely outcome • 23 weeks Open to opinion - precedence given to parents wishes • 24 weeks Resuscitation, unless parents and clinicians agree in the light of the baby’s condition that not in babies best interests • 25 weeks Resuscitation, unless severe abnormality (or very poor condition at birth) incompatible with any significant period of survival (Chiswick, Infant 2008)

35. Neonatal Resuscitation (ELBW Births)AAP/AHA Guidelines for Resuscitation, 5th Edition, 2006 • Where almost certain early death & unacceptably high morbidity likely among rare survivors, non-initiation of resuscitation in delivery room appropriate for conditions such as: • confirmed gestation less than 23 weeks or birth weight less than 400 gram (may exceptions to comply with parental request) • Uncertain prognosis - confirmed gestation of 23-24 weeks, parents views should be supported

36. CONCLUSION (1)Management of extremely preterm birth • Informed counseling of the mother and her family required before birth of a “threshold viability” infant Fetuses and newborn infants at the threshold of viability: a framework for practice. British Association Perinatal Medicine (BAPM) 2000 Thames Regional Perinatal Group. Guidelines related to the birth of extremely immature babies (22-26 weeks gestation) BAPM 2000 • Treatment of all infants with GA of 22 to 26 weeks should be tailored to the infant and family, parents should be fully informed Canadian Paediatric Society. CMAJ 1994

37. CONCLUSION (2) What we do at the Rotunda Hospital, Dublin Considering current mortality and morbidity, “aggressive resuscitation of infants born at 25 weeks gestation is indicated, but not those born at 22 weeks” Allen et al, N Engl J Med 2003

38. Having an infant born extremely prematurely is a very stressful and frightening experience for parents On the one hand, there is an up to 10% risk that their baby will have a life of continuing total dependency On the other hand, most children who survive, even if they have some disabilities, enjoy life and are a source of pleasure to their parents

40. Survival rates have improved but short term morbidity rates at 18 to 30 months have not • Recent (1996–2002) studies developmental and behavioural outcomes • Outcomes ranged from: • Educational attainment and cognitive function • Behaviour and attention problems • Psychiatric problems • Risk taking and criminal behaviours • Increased rates of neuro-developmental & sensory disability Davis DW. Cognitive outcome in school-age children born prematurely. NeontalNetw 2003