Erika F Fernandez MD Assistant Professor Department of Pediatrics, Division of Neonatology

1. Adrenal function in critically ill term newborn infants Erika F Fernandez MD Assistant Professor Department of Pediatrics, Division of Neonatology

2. Background • Many intubated late preterm and term newborns will receive fluid boluses & vasopressors for hypotension • The etiology of hypotension in many infants is unclear • In other critically ill populations: • Hypotension and shock have been linked to : “relative adrenal insufficiency” cortisol < 15 mcg/dl acute stress • Glucocorticoids have significantly ↓ mortality & morbidity in large RCTs Lamberts et al, NEJM 337:1285, 1997

3. Evidence for AI in term newborns Small observational studies • 10 infants with diaphragmatic hernia: 79% of cortisol values <7mcg/dl • Pittinger and Sawin, J Pediatr Surg 35:223, 2000 • 5 of 6 infants with hypotension refractory to vasopressors had cortisol values < 10mcg/dl, BP improved in assoc. with dexamethasone • Tantivit et al, J Perinatol 19:352, 1999

4. Prevalence of low cortisol values • Retrospective chart review • ≥ 35 weeks GA with cortisol values • Critically ill: Intubated, mechanically ventilated and on vasopressors for hypotension Fernandez and Watterberg et al, J Perinatol 25:114, 2005 Data are mean +_ SD or median (25%-75%) 3 infants died (1 MAS, 1 HLHS, 1 CHD)

5. Physiologic response to hydrocortisone • Critically ill hypotensive infants treated w/ hydrocortisone, • Cortisol <15mcg/dl (▲) compared to Cortisol ≥ 15 mcg/dl (O) • Cortisol <15mcg/dl responded to HC with • ↓ dopamine support • ↓ heart rate • ↓ volume expanders Fernandez, Watterberg et al. J Perinatol 25:114, 2005

6. Prospective observational study of term and late preterm critically ill newborns Median [25%-75% percentile] P-value= critically ill infants not receiving vasopressors vs. those receiving vasopressors * = P < 0.05 Fernandez, Montman, Watterberg. 2008, unpublished data

7. No correlation between measures of severity of illness and cortisol values Fernandez, Montman, Watterberg, 2008, unpublished data

8. Summary • High incidence of Rx for hypotension in mechanically ventilated term and late preterm infants • Transitional relative adrenal insufficiency appears to be associated with cardiovascular instability in this population • Prospective observational data consistent with this hypothesis • There are no randomized controlled trials of hydrocortisone for the treatment of hypotension • Plan: multicenter RCT of hydrocortisone for hypotension • We have submitted a proposal for a multicenter observational study through NIH/NICHD/NRN ( currently undergoing budget approval ) to collect baseline data for the final design of such as RCT

9. Mentors and Collaborators • Kristi Watterberg, MD Professor Pediatrics, Division of Neonatology, Mentor, Principal Investigator for Neonatal Research Network (NIH/NICHD/NRN)site at UNM • Robin Ohls, MD, Professor Pediatrics, Division of Neonatology, Co-Principal Investigator for NRN site at UNM • Rebecca Montman, RN, GCRC Research Nurse • Conra Backstrom, RN, GCRC Research Nurse • GCRC statistics, Ronald Schrader, PhD • Administrative support, Green Carlson