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Arch Dis Child Fetal Neonatal Ed. Mar 2005; 90(2): F134–F140.
PMCID: PMC1721849

The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth


Aims: To describe perinatal factors associated with later morbidity among extremely preterm children at 30 months of age corrected for prematurity.

Population: Of 308 surviving children born at [less-than-or-eq, slant]25 weeks gestation in the United Kingdom and Ireland from March to December 1995, 283 (92%) were evaluated at 30 months of age corrected for prematurity.

Methods: Cerebral palsy, severe motor disability, and Bayley scores were used as dependent variables in sequential multiple regression analyses to identify factors associated with adverse outcomes.

Results: Adverse outcomes were consistently more common in boys. Factors related to perinatal illness, ultrasound evidence of brain injury, and treatment (particularly postnatal steroids) were associated with adverse motor outcomes (cerebral palsy, disability or Bayley psychomotor development index). Increasing duration of postnatal steroid treatment was associated with poor motor outcomes. A score was developed for severe motor disability with good negative predictive value. In contrast, mental development was associated with a broader range of factors: ethnic group, maternal educational level, the use of antenatal steroids, and prolonged rupture of membranes in addition to chronic lung disease.

Conclusion: Male sex is a pervasive risk factor for poor outcome at extremely low gestations. Avoidable or effective treatment factors are identified, which may indicate the potential for improving outcome.

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Selected References

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  • Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR. Neurologic and developmental disability after extremely preterm birth. EPICure Study Group. N Engl J Med. 2000 Aug 10;343(6):378–384. [PubMed]
  • Vohr BR, Wright LL, Dusick AM, Mele L, Verter J, Steichen JJ, Simon NP, Wilson DC, Broyles S, Bauer CR, et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993-1994. Pediatrics. 2000 Jun;105(6):1216–1226. [PubMed]
  • Hagberg B, Hagberg G, Beckung E, Uvebrant P. Changing panorama of cerebral palsy in Sweden. VIII. Prevalence and origin in the birth year period 1991-94. Acta Paediatr. 2001 Mar;90(3):271–277. [PubMed]
  • Pharoah PO, Platt MJ, Cooke T. The changing epidemiology of cerebral palsy. Arch Dis Child Fetal Neonatal Ed. 1996 Nov;75(3):F169–F173. [PMC free article] [PubMed]
  • Murphy DJ, Sellers S, MacKenzie IZ, Yudkin PL, Johnson AM. Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies. Lancet. 1995 Dec 2;346(8988):1449–1454. [PubMed]
  • Kuban KC, Leviton A. Cerebral palsy. N Engl J Med. 1994 Jan 20;330(3):188–195. [PubMed]
  • Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics. 2000 Oct;106(4):659–671. [PubMed]
  • Amiel-Tison C, Stewart A. Follow up studies during the first five years of life: a pervasive assessment of neurological function. Arch Dis Child. 1989 Apr;64(4 Spec No):496–502. [PMC free article] [PubMed]
  • BAX MC. TERMINOLOGY AND CLASSIFICATION OF CEREBRAL PALSY. Dev Med Child Neurol. 1964 Jun;6:295–297. [PubMed]
  • Cooke RW. Cerebral palsy in very low birthweight infants. Arch Dis Child. 1990 Feb;65(2):201–206. [PMC free article] [PubMed]
  • Dammann O, Leviton A. Does prepregnancy bacterial vaginosis increase a mother's risk of having a preterm infant with cerebral palsy? Dev Med Child Neurol. 1997 Dec;39(12):836–840. [PubMed]
  • Wu YW, Colford JM., Jr Chorioamnionitis as a risk factor for cerebral palsy: A meta-analysis. JAMA. 2000 Sep 20;284(11):1417–1424. [PubMed]
  • Hitti J, Tarczy-Hornoch P, Murphy J, Hillier SL, Aura J, Eschenbach DA. Amniotic fluid infection, cytokines, and adverse outcome among infants at 34 weeks' gestation or less. Obstet Gynecol. 2001 Dec;98(6):1080–1088. [PubMed]
  • Volpe JJ. Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res. 2001 Nov;50(5):553–562. [PubMed]
  • Zupan V, Gonzalez P, Lacaze-Masmonteil T, Boithias C, d'Allest AM, Dehan M, Gabilan JC. Periventricular leukomalacia: risk factors revisited. Dev Med Child Neurol. 1996 Dec;38(12):1061–1067. [PubMed]
  • Perlman JM. White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome. Early Hum Dev. 1998 Dec;53(2):99–120. [PubMed]
  • Hack M, Wilson-Costello D, Friedman H, Taylor GH, Schluchter M, Fanaroff AA. Neurodevelopment and predictors of outcomes of children with birth weights of less than 1000 g: 1992-1995. Arch Pediatr Adolesc Med. 2000 Jul;154(7):725–731. [PubMed]
  • Gray PH, Jones P, O'Callaghan MJ. Maternal antecedents for cerebral palsy in extremely preterm babies: a case-control study. Dev Med Child Neurol. 2001 Sep;43(9):580–585. [PubMed]
  • Jobe AH. Glucocorticoids, inflammation and the perinatal lung. Semin Neonatol. 2001 Aug;6(4):331–342. [PubMed]
  • Watts DH, Krohn MA, Hillier SL, Eschenbach DA. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol. 1992 Mar;79(3):351–357. [PubMed]
  • Smulian JC, Shen-Schwarz S, Vintzileos AM, Lake MF, Ananth CV. Clinical chorioamnionitis and histologic placental inflammation. Obstet Gynecol. 1999 Dec;94(6):1000–1005. [PubMed]
  • Leviton A, Paneth N. White matter damage in preterm newborns--an epidemiologic perspective. Early Hum Dev. 1990 Oct;24(1):1–22. [PubMed]
  • Cooke RW. Early and late cranial ultrasonographic appearances and outcome in very low birthweight infants. Arch Dis Child. 1987 Sep;62(9):931–937. [PMC free article] [PubMed]
  • Pinto-Martin JA, Riolo S, Cnaan A, Holzman C, Susser MW, Paneth N. Cranial ultrasound prediction of disabling and nondisabling cerebral palsy at age two in a low birth weight population. Pediatrics. 1995 Feb;95(2):249–254. [PubMed]
  • Reynolds PR, Dale RC, Cowan FM. Neonatal cranial ultrasound interpretation: a clinical audit. Arch Dis Child Fetal Neonatal Ed. 2001 Mar;84(2):F92–F95. [PMC free article] [PubMed]
  • Pierrat V, Duquennoy C, van Haastert IC, Ernst M, Guilley N, de Vries LS. Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leucomalacia. Arch Dis Child Fetal Neonatal Ed. 2001 May;84(3):F151–F156. [PMC free article] [PubMed]
  • Barrington KJ. Hazards of systemic steroids for ventilator-dependent preterm infants: what would a parent want? CMAJ. 2001 Jul 10;165(1):33–34. [PMC free article] [PubMed]
  • Doyle L, Davis P, Morley C. Risks and benefits of steroids in preterm infants. J Pediatr. 2001 May;138(5):784–786. [PubMed]
  • Doyle L, Davis P. Postnatal corticosteroids in preterm infants: systematic review of effects on mortality and motor function. J Paediatr Child Health. 2000 Apr;36(2):101–107. [PubMed]
  • Yeh TF, Lin YJ, Huang CC, Chen YJ, Lin CH, Lin HC, Hsieh WS, Lien YJ. Early dexamethasone therapy in preterm infants: a follow-up study. Pediatrics. 1998 May;101(5):E7–E7. [PubMed]
  • Stark AR, Carlo WA, Tyson JE, Papile LA, Wright LL, Shankaran S, Donovan EF, Oh W, Bauer CR, Saha S, et al. Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 2001 Jan 11;344(2):95–101. [PubMed]
  • Garg M, Kurzner SI, Bautista DB, Keens TG. Clinically unsuspected hypoxia during sleep and feeding in infants with bronchopulmonary dysplasia. Pediatrics. 1988 May;81(5):635–642. [PubMed]
  • Durand M, McEvoy C, MacDonald K. Spontaneous desaturations in intubated very low birth weight infants with acute and chronic lung disease. Pediatr Pulmonol. 1992 Jul;13(3):136–142. [PubMed]
  • Ment LR, Schwartz M, Makuch RW, Stewart WB. Association of chronic sublethal hypoxia with ventriculomegaly in the developing rat brain. Brain Res Dev Brain Res. 1998 Dec 7;111(2):197–203. [PubMed]
  • Takashima S, Becker LE. Developmental neuropathology in bronchopulmonary dysplasia: alteration of glial fibrillary acidic protein and myelination. Brain Dev. 1984;6(5):451–457. [PubMed]
  • Hargitai B, Szabó V, Hajdú J, Harmath A, Pataki M, Farid P, Papp Z, Szende B. Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants. Pediatr Res. 2001 Jul;50(1):110–114. [PubMed]
  • Vohr BR, Coll CG, Lobato D, Yunis KA, O'Dea C, Oh W. Neurodevelopmental and medical status of low-birthweight survivors of bronchopulmonary dysplasia at 10 to 12 years of age. Dev Med Child Neurol. 1991 Aug;33(8):690–697. [PubMed]
  • Vrlenich LA, Bozynski ME, Shyr Y, Schork MA, Roloff DW, McCormick MC. The effect of bronchopulmonary dysplasia on growth at school age. Pediatrics. 1995 Jun;95(6):855–859. [PubMed]
  • Northway WH, Jr, Moss RB, Carlisle KB, Parker BR, Popp RL, Pitlick PT, Eichler I, Lamm RL, Brown BW., Jr Late pulmonary sequelae of bronchopulmonary dysplasia. N Engl J Med. 1990 Dec 27;323(26):1793–1799. [PubMed]
  • Hack M, Taylor HG, Klein N, Eiben R, Schatschneider C, Mercuri-Minich N. School-age outcomes in children with birth weights under 750 g. N Engl J Med. 1994 Sep 22;331(12):753–759. [PubMed]
  • O'Shea TM, Goldstein DJ, deRegnier RA, Sheaffer CI, Roberts DD, Dillard RG. Outcome at 4 to 5 years of age in children recovered from neonatal chronic lung disease. Dev Med Child Neurol. 1996 Sep;38(9):830–839. [PubMed]
  • Singer L, Yamashita T, Lilien L, Collin M, Baley J. A longitudinal study of developmental outcome of infants with bronchopulmonary dysplasia and very low birth weight. Pediatrics. 1997 Dec;100(6):987–993. [PMC free article] [PubMed]
  • Böhm B, Katz-Salamon M. Cognitive development at 5.5 years of children with chronic lung disease of prematurity. Arch Dis Child Fetal Neonatal Ed. 2003 Mar;88(2):F101–F105. [PMC free article] [PubMed]
  • Bowen JR, Starte DR, Arnold JD, Simmons JL, Ma PJ, Leslie GI. Extremely low birthweight infants at 3 years: a developmental profile. J Paediatr Child Health. 1993 Aug;29(4):276–281. [PubMed]
  • Katz-Salamon M, Gerner EM, Jonsson B, Lagercrantz H. Early motor and mental development in very preterm infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed. 2000 Jul;83(1):F1–F6. [PMC free article] [PubMed]
  • Agarwal R, Chiswick ML, Rimmer S, Taylor GM, McNally RJQ, Alston RD, D'Souza SW. Antenatal steroids are associated with a reduction in the incidence of cerebral white matter lesions in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2002 Mar;86(2):F96–F101. [PMC free article] [PubMed]
  • Baud O, Foix-L'Helias L, Kaminski M, Audibert F, Jarreau PH, Papiernik E, Huon C, Lepercq J, Dehan M, Lacaze-Masmonteil T. Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants. N Engl J Med. 1999 Oct 14;341(16):1190–1196. [PubMed]
  • Duncan GJ, Brooks-Gunn J, Klebanov PK. Economic deprivation and early childhood development. Child Dev. 1994 Apr;65(2 Spec No):296–318. [PubMed]
  • Jefferis Barbara J M H, Power Chris, Hertzman Clyde. Birth weight, childhood socioeconomic environment, and cognitive development in the 1958 British birth cohort study. BMJ. 2002 Aug 10;325(7359):305–305. [PMC free article] [PubMed]
  • Fawer CL, Besnier S, Forcada M, Buclin T, Calame A. Influence of perinatal, developmental and environmental factors on cognitive abilities of preterm children without major impairments at 5 years. Early Hum Dev. 1995 Oct 2;43(2):151–164. [PubMed]
  • Lee H, Barratt MS. Cognitive development of preterm low birth weight children at 5 to 8 years old. J Dev Behav Pediatr. 1993 Aug;14(4):242–249. [PubMed]
  • Sommerfelt K, Ellertsen B, Markestad T. Parental factors in cognitive outcome of non-handicapped low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1995 Nov;73(3):F135–F142. [PMC free article] [PubMed]
  • Landry Susan H, Smith Karen E, Swank Paul R. Environmental effects on language development in normal and high-risk child populations. Semin Pediatr Neurol. 2002 Sep;9(3):192–200. [PubMed]

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