Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Neuropsychological and behavioral effects of postnatal dexamethasone in extremely low birth weight preterm children at early school age

Journal of Perinatology volume 32, pages 139–146 (2012)Cite this article

Abstract

Objective:

To study postnatal dexamethasone treatment effects on cognitive, neuropsychological and behavioral functioning at early school age in preterm children.

Study Design:

We recruited 222 children born between 1998 and 2003: 114 extremely low birth weight (<1000 g; 60 dexamethasone-treated; 54 untreated) and 108 term-born. Data were analyzed using multivariate methods.

Result:

Preterm performed below term-born on all measures. Dexamethasone-treated performed below dexamethasone-untreated in immediate visual memory, visual-motor integration, mathematical skill and motor dexterity. However, stepwise regression indicated that medical and sociodemographic factors other than dexamethasone contributed to preterm group differences.

Conclusion:

Dexamethasone alone does not explain neurocognitive impairment in preterm children. Medical and sociodemographic factors (illness severity, male gender and parental education) are influential. Prospective longitudinal neuropsychological and behavioral study from preschool to school age that considers medical and sociodemographic variables will best address effects of dexamethasone exposure.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kreider ML, Tate CA, Cousins MM, Oliver CA, Seidler FJ, Slotkin TA et al. Lasting effects of developmental dexamethasone treatment on neural cell number and size, synaptic activity, and cell signaling: critical periods of vulnerability, dose-effect relationships, regional targets, and sex selectivity. Neuropsychopharmacology 2006; 31 (1): 12–35.

    Article  CAS  Google Scholar 

  2. Brozanski BS, Jones JG, Gilmour CH, Balsan MJ, Vazquez RL, Israel BA et al. Effect of pulse dexamethasone therapy on the incidence and severity of chronic lung disease in the very low birth weight infant. J Pediatr 1995; 126 (5 Part 1): 769–776.

    Article  CAS  Google Scholar 

  3. Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB . Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics 2006; 117 (1): 75–83.

    Article  Google Scholar 

  4. Halliday HL . Clinical trials of postnatal corticosteroids: inhaled and systemic. Biol Neonate 1999; 76 (Suppl 1): 29–40.

    Article  CAS  Google Scholar 

  5. Halliday HL, Patterson CC, Halahakoon CW . A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: comparison of early and late treatment and of dexamethasone and inhaled budesonide. Pediatrics 2001; 107 (2): 232–240.

    Article  CAS  Google Scholar 

  6. Raman L, Georgieff MK, Rao R . The role of chronic hypoxia in the development of neurocognitive abnormalities in preterm infants with bronchopulmonary dysplasia. Dev Sci 2006; 9 (4): 359–367.

    Article  Google Scholar 

  7. Thompson DK, Warfield SK, Carlin JB, Pavlovic M, Wang HX, Bear M et al. Perinatal risk factors altering regional brain structure in the preterm infant. Brain 2007; 130 (Part 3): 667–677.

    Article  Google Scholar 

  8. Barrington KJ . The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. BMC Pediatr 2001; 1: 1.

    Article  CAS  Google Scholar 

  9. Doyle LW, Ehrenkranz RA, Halliday HL . Dexamethasone treatment in the first week of life for preventing bronchopulmonary dysplasia in preterm infants: a systematic review. Neonatology 2010; 98 (3): 217–224.

    Article  CAS  Google Scholar 

  10. Grier DG, Halliday HL . Corticosteroids in the prevention and management of bronchopulmonary dysplasia. Semin Neonatol 2003; 8 (1): 83–91.

    Article  Google Scholar 

  11. Needelman H, Evans M, Roberts H, Sweney M, Bodensteiner JB . Effects of postnatal dexamethasone exposure on the developmental outcome of premature infants. J Child Neurol 2008; 23 (4): 421–424.

    Article  Google Scholar 

  12. Cummings JJ, D’Eugenio DB, Gross SJ . A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia. N Engl J Med 1989; 320 (23): 1505–1510.

    Article  CAS  Google Scholar 

  13. Onland W, van Kaam AH, De Jaegere AP, Offringa M . Open-label glucocorticoids modulate dexamethasone trial results in preterm infants. Pediatrics 2010; 126 (4): e954–e964.

    Article  Google Scholar 

  14. Romagnoli C, Zecca E, Luciano R, Torrioli G, Tortorolo G . Controlled trial of early dexamethasone treatment for the prevention of chronic lung disease in preterm infants: a 3-year follow-up. Pediatrics 2002; 109 (6): e85.

    Article  Google Scholar 

  15. Baud O . Is perinatal dexamethasone treatment safe in preterm infants? Dev Med Child Neurol Suppl 2001; 86: 23–25.

    CAS  PubMed  Google Scholar 

  16. McEwen BS . Steroid hormones and brain development: some guidelines for understanding actions of pseudohormones and other toxic agents. Environ Health Perspect 1987; 74: 177–184.

    Article  CAS  Google Scholar 

  17. Murphy BP, Inder TE, Huppi PS, Warfield S, Zientara GP, Kikinis R et al. Impaired cerebral cortical gray matter growth after treatment with dexamethasone for neonatal chronic lung disease. Pediatrics 2001; 107 (2): 217–221.

    Article  CAS  Google Scholar 

  18. American_Academy_of_Pediatrics. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants. Pediatrics 2002; 109 (2): 330–338.

    Article  Google Scholar 

  19. Watterberg KL . Postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia. Pediatrics 2010; 126 (4): 800–808.

    Article  Google Scholar 

  20. Hintz SR, Kendrick DE, Vohr BR, Poole WK, Higgins RD . Changes in neurodevelopmental outcomes at 18 to 22 months’ corrected age among infants of less than 25 weeks’ gestational age born in 1993-1999. Pediatrics 2005; 115 (6): 1645–1651.

    Article  Google Scholar 

  21. Short EJ, Klein NK, Lewis BA, Fulton S, Eisengart S, Kercsmar C et al. Cognitive and academic consequences of bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes. Pediatrics 2003; 112 (5): e359.

    Article  Google Scholar 

  22. Thompson DK, Wood SJ, Doyle LW, Warfield SK, Lodygensky GA, Anderson PJ et al. Neonate hippocampal volumes: prematurity, perinatal predictors, and 2-year outcome. Ann Neurol 2008; 63 (5): 642–651.

    Article  Google Scholar 

  23. Gross SJ, Anbar RD, Mettelman BB . Follow-up at 15 years of preterm infants from a controlled trial of moderately early dexamethasone for the prevention of chronic lung disease. Pediatrics 2005; 115: 681–687.

    Article  Google Scholar 

  24. Jones R, Wincott E, Elbourne D, Grant A . Controlled trial of dexamethasone in neonatal chronic lung disease: a 3-year follow-up. Pediatrics 1995; 96 (5 Part 1): 897–906.

    CAS  PubMed  Google Scholar 

  25. O’Shea TM, Washburn LK, Nixon PA, Goldstein DJ . Follow-up of a randomized, placebo-controlled trial of dexamethasone to decrease the duration of ventilator dependency in very low birth weight infants: neurodevelopmental outcomes at 4 to 11 years of age. Pediatrics 2007; 120 (3): 594–602.

    Article  Google Scholar 

  26. Yeh TF, Lin YJ, Lin HC, Huang CC, Hsieh WS, Lin CH et al. Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 2004; 12: 363–373.

    Google Scholar 

  27. Elliott CD . Differential Ability Scales. The Psychological Corporation: San Anontio, TX, 1990.

    Google Scholar 

  28. Wechsler D . Wechsler Intelligence Scale for Children, 4th edn. The Psychological Corporation: San Antonio, TX, 2003.

    Google Scholar 

  29. Farrell Pagulayan K, Busch RM, Medina KL, Bartok JA, Krikorian R . Developmental normative data for the Corsi Block-tapping task. J Clin Exp Neuropsychol 2006; 28 (6): 1043–1052.

    Article  Google Scholar 

  30. Beery KE, Beery NA . The Beery-Buktenica Developmental Test of Visual-Motor Integration: Administration, Scoring, and Teaching Manual. Pearson Inc.: Minneapolis, MN, 2004.

    Google Scholar 

  31. Gardner RA, Broman M . The Purdue Pegboard: Normative data on 1334 school children. J Clin Child Psychol 1979; 1: 156–162.

    Article  Google Scholar 

  32. Manly T, Robertson IH, Anderson V, Nimmo-Smith I . The Test of Everyday Attention for Children: Manual. Thames Valley Test Company Limited: Bury St Edmunds, 1999.

    Google Scholar 

  33. Wagner RK, Torgesen JK, Rashotte CA . Examiner's Manual: The Comprehensive Test of Phonological Processing. PRO-ED Inc.: Austin, TX, 1999.

    Google Scholar 

  34. Baron IS . Neuropsychological Evaluation of the Child. Oxford University Press: New York, 2004.

    Google Scholar 

  35. Gioia GA, Isquith PK, Guy SC, Kenworthy L . Behavior Rating Inventory of Executive Function. Psychological Assessment Resources Inc.: Odessa, FL, 2000.

    Google Scholar 

  36. Reynolds C, Kamphaus RW . Behavior Assessment System for Children-2. American Guidance Services Inc.: Circle Pines, MN, 1998.

    Google Scholar 

  37. Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJ . Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002; 288 (6): 728–737.

    Article  Google Scholar 

  38. Baron IS, Ahronovich MD, Erickson K, Gidley Larson JC, Litman FR . Age-appropriate early school age neurobehavioral outcomes of extremely preterm birth without severe intraventricular hemorrhage: a single center experience. Early Hum Dev 2009; 85: 191–196.

    Article  Google Scholar 

  39. Edgin JO, Inder TE, Anderson PJ, Hood KM, Clark CA, Woodward LJ . Executive functioning in preschool children born very preterm: relationship with early white matter pathology. J Int Neuropsychol Soc 2008; 14 (1): 90–101.

    Article  Google Scholar 

  40. Shinwell ES, Karplus M, Reich D, Weintraub Z, Blazer S, Bader D,et al. Early postnatal dexamethasone treatment and increased incidence of cerebral palsy. Arch Dis Child Fetal Neonatal Ed 2000; 83 (3): F177–F181.

    Article  CAS  Google Scholar 

  41. Halliday HL, Ehrenkranz RA, Doyle LW . Early (&lt;8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 2010; (1) CD001146.

  42. Halliday HL, Ehrenkranz RA, Doyle LW . Late (&gt;7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev 2009; (1) CD001145.

  43. Marlow N, Wolke D, Bracewell M, Samara M . Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 2005; 325: 9–19.

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by an Inova Health Systems Faculty Grant awarded to one of the authors (ISB), and by the Maggie Snyder Foundation for the Premature and Pediatric Pulmonary Patient of Falls Church, VA. We gratefully acknowledge the assistance of Rebecca Q Beck and Donna Long, and the support of Margaret Snyder.

Author information

Authors and Affiliations

  1. Fairfax Neonatal Associates, Inova Fairfax Hospital for Children, Falls Church, VA, USA

    K C Crotty, M D Ahronovich, I S Baron, R Baker, K Erickson & F R Litman

  2. Department of Pediatrics, Inova Fairfax Hospital for Children, Falls Church, VA, USA

    M D Ahronovich, I S Baron, R Baker & F R Litman

Authors
  1. K C Crotty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M D Ahronovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I S Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Erickson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F R Litman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I S Baron.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crotty, K., Ahronovich, M., Baron, I. et al. Neuropsychological and behavioral effects of postnatal dexamethasone in extremely low birth weight preterm children at early school age. J Perinatol 32, 139–146 (2012). https://doi.org/10.1038/jp.2011.62

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2011.62

Keywords

Search

Advanced search

Quick links