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Postnatal Steroids 2005

Postnatal Steroids 2005. Eric S. Shinwell, MD Kaplan Medical Center Rehovot Hebrew University Jerusalem, Israel. Recent History. 1997-2001 : Reports of adverse neurologic effects of Dexamethasone (Yeh 1997, Shinwell 1998, O’Shea 1998)

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Postnatal Steroids 2005

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  1. Postnatal Steroids 2005 Eric S. Shinwell, MD Kaplan Medical Center Rehovot Hebrew University Jerusalem, Israel

  2. Recent History • 1997-2001: Reports of adverse neurologic effects of Dexamethasone (Yeh 1997, Shinwell 1998, O’Shea 1998) • 2002: Guidelines from American Academy of Pediatrics and Canadian Pediatric Society • 2005: New data: Follow-up studies, The “Fear of Steroids” Era

  3. 2005: Latest news • Clinical • Laboratory / Imaging • Coping Strategies

  4. Steroids reduce BPD at 36 weeks Odds Ratio Decreased Risk Increased OUTCOME VARIABLE ( 95% CI ) 0.2 0.5 1.0 2.0 4.0 EARLY 0.69 (0.60-0.80) (<4 days) MODERATELY-EARLY 0.62 (0.47-0.82) (1-2 wks) 0.76 (0.58-1.00) DELAYED (>2 wks) 0.2 0.5 1.0 2.0 4.0 Odds Ratio and 95% CI Halliday, Ehrenkrantz, Doyle, 2003

  5. No Effect on Mortality Odds Ratio Decreased Risk Increased OUTCOME VARIABLE ( 95% CI ) 0.2 0.5 1.0 2.0 4.0 EARLY 1.02 (0.90-1.17) MODERATELY-EARLY 0.66 (0.40-1.09) 1.03 (0.71-1.50) DELAYED 0.2 0.5 1.0 2.0 4.0 Odds Ratio and 95% CI Halliday, Ehrenkrantz, Doyle, 2003

  6. CEREBRAL PALSY Odds Ratio Decreased Risk Increased OUTCOME VARIABLE ( 95% CI ) 0.2 0.5 1.0 2.0 4.0 EARLY 1.69 (1.20-2.38) MODERATELY-EARLY 0.83 (0.39-1.74) 1.20 (0.77-1.85) DELAYED 0.2 0.5 1.0 2.0 4.0 Odds Ratio and 95% CI Halliday, Ehrenkrantz, Doyle, 2003

  7. School-age Follow-up • RCT, Early, 4-wks Dex • F/U at 8 years • Dex: • Lower Height and HC • More motor dysfunction • Lower cognition scores on WISC-II • Higher Total Impairment Scores Yeh et al, NEJM 2004

  8. Follow-up: 8 years • Washburn, O’Shea, SPR 2004 • Moderately-early, 42 day Dex, n = 38 dex, 30 placeboAdverse effect neuro 2 yrs • 8 yrs, No effect on: • Growth • BP • Cognitive Function • Adaptive Behavior

  9. Follow-up: 15 years • Gross, et al. • <1250 g, Ventilated at 2 weeks • Dex 42 days vs 18 days vs placebo • 22 of 36 survived • Intact survival: • 42d: 69%; 18d:25%; Placebo: 18% • Pulmonary function best in 42d. Pediatrics 2005;115:681-687

  10. Collaborative Dex Trial • Dex 1/52, after age 2/52, Open-label Dex • 13-17 year Follow-up (n=150) • Neuro (↓), Psych, Education (↓) • Growth (↓), Respiratory (↓), BP (↑) • No major differences • Trend to more CP (OR 1.58 0.81-3.07) Pediatrics 2005;116:370-384

  11. Is there a scientific basis to steroid neurotoxicity?

  12. Effect on Neurodevelopment: Animal Models • Plint, et al: Systematic Review • Animal models, Controlled trial, growth and neurodevelopment • n = 98 • Growth restriction universal • Neuro results highly variable

  13. Brain Growth • Quantitative MRI in preterm infants at term • 7 Dex, 11 Control, 14 term • Dex-treated had 35% less cortical grey matter • Other areas not affected Murphy, et al. Pediatrics 2001;107:217

  14. Latest Volume MRI Studies • Pavlovic, Inder (SPR ’05):BW <1250, n=83, multivar. analysisDex: Changed frontal microstructure(Apparent Diffusion Coefficient, Fractional Anisotropy)Males: regional gray matter reduction • Parikh (SPR ’05):ELBW, n=34, Dex, corrected for GAReduced Overall Cortical Volume

  15. Latest Volume MRI Studies • Pavlovic, Inder (SPR ’05):BW <1250, n=83, multivar. analysisDex: Changed frontal microstructure(Apparent Diffusion Coefficient, Fractional Anisotropy)Males: regional gray matter reduction • Parikh (SPR ’05):ELBW, n=34, Dex, corrected for GAReduced Overall Cortical Volume

  16. Brain Volumes: Hydrocortisone • Observational study of brain volumes (MRI) • 8 year old former premies, n=58 • +/- Hydrocortisone • low dose (5mg/kg/day, tapered over 3 weeks) • No effect of Hydrocortisone on White or Grey Matter or Hippocampal size • Preterm infants: lower grey and white matter volumes than term infants Lodygensky, de Vries, Huppi, 2005

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