1. Ethics in the Delivery Room C0009 NRP® Current Issues Seminar: Monumental Changes on the Horizon Steven Ringer, MD, PhD, FAAPHenry C. Lee, MD, FAAP Massachusetts General HospitalStanford University (Boston, MA)(Palo Alto, CA)

2. Faculty Disclosure Information In the past 12 months, we have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity. We do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.

3. Learning Objectives Review NRP Guidelines for Withholding and Discontinuing Resuscitation Become familiar with common scenarios presenting ethical conflict in neonatal resuscitation Understand divergent perspectives for ethical modes of shared decision-making for: – preterm neonates in the gray zone of periviable birth – non-responsive term infant Recognize the issues surrounding research during the newborn period

4. Case #1 A woman presents at 23 +4/7 weeks gestation with preterm labor and cervical dilation. She has some uterine tenderness but no other signs of chorioamnionitis. You meet with her and her partner to discuss care of the fetus / newborn as delivery appears to be imminent

5. Case #1 How do you counsel the family? What options do you discuss? What else would you like to know?

6. Case #1 Periviable birth: executive summary of a joint workshop by the Eunice Kennedy Shriver NICHD, SMFM, AAP, ACOG. Variability across populations and centers – Antenatal and neonatal practices – Outcomes Importance of communication between obstetric and neonatal teams Raju T, Mercer B, Burchfield D, Joseph G. AJOG. 2014; 210(5):406-17.

7. Case #1 AuthorsTimeSurvival (%) 22 weeks Survival (%) 23 weeks Survival (%) 24 weeks Survival (%) 25 weeks Donohue1993-200131 Petrova1998-200140 Tyson1998-200351 Mehler2000-200741768280 Kyser2000-2009335887 Stoll2003-20076265572 Lee2005-200852860

8. Case #1 Obstetric care – should this mother receive / be offered / not receive: – Tocolytic therapy? – Antenatal corticosteroids? – Magnesium sulfate for neuroprotection? – Antibiotic treatment? – Cesarean delivery?

9. Case #1 Tocolysis / magnesium sulfate / antibiotics – no studies specifically address preterm labor at 20-25 weeks GA Corticosteroids – observational studies show benefit for 23 to 25 weeks, but not at 22 weeks. Mortality reduced for all GA

10. Case #1 Cesarean delivery – – Routine? – In fetal distress?

11. Case #1 Components of counseling – Benefits and risks of obstetric interventions – Rationale for or against active maternal and neonatal intevention – Institutional, regional, or other data on outcomes – Comfort care as an approach to care

12. Antenatal Counseling Regarding Resuscitation and Intensive Care Before 25 Weeks of Gestation (COFN 2015) “wait and see” attitude may not be optimal – Not accurate in prediction – Can delay resuscitation Attitude of parents – Statistical information may not be useful for some families

13. ILCOR 2015 However, in individual cases, when counseling a family and constructing a prognosis for survival at gestations below 25 weeks, it is reasonable to consider variables such as perceived accuracy of gestational age assignment, the presence or absence of chorioamnionitis, and the level of care available for location of delivery. Decisions about appropriateness of resuscitation below 25 weeks of gestation will be influenced by region-specific guidelines.

14. Case #2 A mother presents at term gestation with two hours of decreased fetal movement. Rapid ultrasound reveals little movement and a markedly slow heart rate. The patient is taken for immediate cesarean section, and the infant emerges pale and cyanotic with no spontaneous movement or breathing.

15. Case #2 Resuscitation is begun according to NRP guidelines. Despite good chest rise with PPV, giving epinephrine, no heart rate can be palpated or heard, even after 10 minutes of resuscitative efforts. Your team is wondering what to do.

16. Case #2 Is it reasonable to stop resuscitative efforts? What are the possible outcomes? Does it matter what type of hospital where this occurs?

17. Case #2 When is resuscitation futile? – ILCOR 2015 – We suggest that, in infants with an Apgar score of 0 after 10 minutes of resuscitation, if the heart rate remains undetectable, it may be reasonable to stop assisted ventilation;

18. Case #2 …however, the decision to continue or discontinue resuscitative efforts must be individualized. Variables to be considered may include – whether the resuscitation was considered optimal; – availability of advanced neonatal care, such as therapeutic hypothermia; – Specific circumstances before delivery (eg, known timing of the insult); – and wishes expressed by the family

19. Case #2 - ? Futile ? Subgroup analysis of NICHD Cooling trial revealed that 24 % of infants with 10 minute Apgar of 0 were alive without moderate to severe disability at 18 months, 21% with IQ 77-99 and normal executive, visual and motor function at 6-7 years Sarkar et al reported uniformly poor outcome among infants treated with head cooling who had 10 minute Apgar of 0. Sarkar S, Predicting death despite therapeutic hypothermia in infants with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2010;95:F423–8.

20. Case #2 Is 10 minutes enough or too much? Kasdorf and coworkers examined recent studies that included therapeutic hypothermia, and acquired data for infants without apparent HR at 10 minutes: 4 RCTs done between 2000- 2009, and local experience ADC-FNN Online First, published on October 23, 2014 as 10.1136/archdischild-2014-306687

21. * Mortality or abnormal NDI occurred in 73% of infants treated with hypothermia, and 79% of controls. * 15/56 (27%) of those treated with hypothermia, and 7/34 (21%) of normothermic controls were developmentally normal at follow up * Overall mortality was 50%.

22. Case #2 These results, while still limited, are far better than earlier small studies that antedate hypothermia: Jain published series of 58 infants, all but one of whom expired Haddad reported 16 term and preterm infants, of whom 14 expired Intriguing that both cooled and normothermic infants did better

23. Case #2 Beware the limitations… – Selected cohort, not all compared with controls – The most severe cases may not have been offered hypothermia – We don’t know how many babies died in delivery room, and we don’t know details of resuscitation, or what the HR really was – Follow-up is limited to 18-24 months

24. Case #2 The data suggest that outcomes are improving Death in the DR may not be a limitation in that if resuscitation is impossible there is no survival with severe disability. There is also the opportunity to limit care in NICU In high level centers, depending on circumstances, continuing resuscitation may be correct

25. Case #2 How important is HR? – The primary goal of resuscitation is to establish ventilation, but… – the gold standard of assessment is a rise in the Heart Rate – Major errors do occur, including not detecting a HR that is there, or identifying a HR when none is present

26. Case #3 - RESEARCH Was the SUPPORT trial unethical? What could have been done better in regard to informed consent? Were there errors in the judgment of the Office for Human Research Protection’s assessment? In ideal circumstances, what could have been improved scientifically to allow better generalizability of results?

27. SUPPORT 23 centers NICHD Low vs high oxygen saturation target – Lower oxygen target  lower risk of ROP – Higher oxygen target  increased survival CPAP vs intubation at birth

28. SUPPORT OHRP – consent forms inadequate due to not informing of “foreseeable risks” New York Times article Lawsuit against UAB Hospital – summary judgment dismissed.

29. SUPPORT – representative enrollment? “Enrollment of extremely low birth weight infants in a clinical research study may not be representative” Wade Rich et al. Pediatrics 2012

30. SUPPORT – representative enrollment? “Enrollment of extremely low birth weight infants in a clinical research study may not be representative” Wade Rich et al. Pediatrics 2012

31. RESEARCH ETHICS You would like to design a research study to test tracheal suctioning for meconium stained amniotic fluid. – What is your study design? Randomized - how? – Who will you enroll? – Will you obtain informed consent / how?

32. Changes You May Wish to Make in Practice 1. Work with an interdisciplinary team to develop policies and procedures to promote consistent yet individualized, timely, effective counseling for periviable birth. 2. Develop strategies for appropriate practice in supporting families in providing comfort care to a neonate when resuscitation is withheld or stopped.

33. References For more information on this subject, see the following publications: Please refer to handouts.