Postnatal steroids 2005
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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

Postnatal Steroids 2005

Eric S. Shinwell, MD

Kaplan Medical Center

Rehovot Hebrew University Jerusalem, Israel


Recent history

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


2005 latest news

2005: Latest news

  • Clinical

  • Laboratory / Imaging

  • Coping Strategies


Postnatal steroids 2005 1357124

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


Postnatal steroids 2005 1357124

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


Postnatal steroids 2005 1357124

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


Postnatal steroids 2005 1357124

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


Follow up 8 years

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


Follow up 15 years

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


Collaborative dex trial

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


Postnatal steroids 2005 1357124

Is there a scientific basis to steroid neurotoxicity?


Effect on neurodevelopment animal models

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


Brain growth

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


Latest volume mri studies

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


Latest volume mri studies1

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


Brain volumes hydrocortisone

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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