European Journal of Pediatrics

, Volume 155, Issue 7, pp 580–588 | Cite as

A randomized trial comparing the effect of prophylactic intravenous fresh frozen plasma, gelatin or glucose on early mortality and morbidity in preterm babies

  • The Northern Neonatal Nursing Initiative [NNNI] Trial Group
  • D. Elbourne
Neonatology

Abstract

Seven hundred and seventy-six children born before 32 weeks gestation between 1990 and 1992 were randomly allocated within 2 h of birth to one of three groups: either prophylactic fresh frozen plasma (20 ml/kg followed by 10 ml/kg after 24 h); or a similar volume of an inert gelatin plasma substitute (Gelofusine); or control management with a maintenance infusion of 10% dextrose. The three groups were similar at trial entry. There were no statistically significant differences in the number of deaths before discharge (fresh frozen plasma 19.1%, gelatin 22.0% and control 17.8%). Death or disability amongst long-term survivors at 2 years of age, is the primary trial outcome variable: this information is not yet available. Death before discharge from hospital or the presence of a cerebral ultrasound scan abnormality 1 or 6 weeks after birth in survivors was a pre-defined secondary outcome variable (although 176 long-term survivors never had a scan, largely because they never needed care in a unit staffed to provide prolonged respiratory support or a routine scan service). Of the children entered into the three arms of the trial, 43.0%, 37.5% and 42.3% respectively died or were known to have developed at least a minor cerebral ultrasound abnormality before discharge. The proportions dead or known to have developed a major scan abnormality (ventriculomegaly or a persisting parenchymal abnormality), were 22.7%, 27.0% and 23.3%.

Key words

Neonate Intraventricular haemorrhage Fresh frozen plasma Gelatin Volume, expansion Randomized controlled trial 

Abbreviations

CI

confidence intervals

IVH

intraventricular haemorrhage

NNNI

Northern Neonatal Nursing Initiative

OSIRIS

Open study of infants at risk of or with respiratory insufficiency—the role of surfactant

RR

relative risks

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References

  1. 1.
    Andrew M, Vegh P, Caco C, Kirpalani H, Jefferies A, Ohlsson A, Watts J, Saigal S, Milner R, Wang E (1993) A randomized controlled trial of platelet infusions in thrombocytopenic premature infants. J Pediatr 123:285–291Google Scholar
  2. 2.
    Barr PA, Bailey PE, Summers J, Cassady G (1977) Relation between arterial blood pressure and blood volume and effect of infused albumin in sick preterm infants. Pediatrics 60:282–289Google Scholar
  3. 3.
    Bauer K, Linderkamp O, Versmold HT (1993) Systolic blood pressure and low blood volume in preterm infants. Arch Dis Child 69:F521–522Google Scholar
  4. 4.
    Beverley DW, Chance GW, Inwood MJ, Schaus M, O'Keefe B (1984) Intraventricular haemorrhage and haemostasis defects. Arch Dis Child 59:444–448Google Scholar
  5. 5.
    Beverley DW, Pitts-Tucker TJ, Congdon PJ, Arthur RJ, Tate G (1985) Prevention of intraventricular haemorrhage by fresh frozen plasma. Arch Dis Child 60:710–713Google Scholar
  6. 6.
    Bignall S, Bailey PC, Bass CA, Cramb R, Rivers RPA, Wadsworth J (1989) The cardiovascular and oncotic effects of albumin infusion in premature infants. Early Hum Dev 20:191–201Google Scholar
  7. 7.
    Cohen H (1993) Avoiding the misuse of fresh frozen plasma. BMJ 307:395–396Google Scholar
  8. 8.
    Cooke RWI (1991) Trends in preterm survival and incidence of cerebral haemorrhage. Arch Dis Child 66:403–407Google Scholar
  9. 9.
    EC Ethamsylate trial group (1994) The EC randomized controlled trial of prophylactic ethamsylate for very preterm neonates: early mortality and morbidity. Arch Dis Child 70:F201-F205Google Scholar
  10. 10.
    Elbourne DR (1994) Early cord clamping in preterm infants. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (eds) Pregnancy and childbirth, module. “Cochrane Database of Systematic Reviews”: Review No. 05944, 22 June 1993. Published through “Cochrane Updates on Disk”, Oxford: Update Software 1994 Disk Issue 1Google Scholar
  11. 11.
    Emery EF, Greenough A (1993) Efficacy of low-dose dopamine infusion. Acta Paediatr 82:430–432Google Scholar
  12. 12.
    Gill AB, Weindling AM (1993) Randomized controlled trial of plasma protein fraction versus dopamine in hypotensive very low birthweight infants. Arch Dis Child 69:284–287Google Scholar
  13. 13.
    Gray OP, Ackerman A, Fraser AJ (1968) Intracranial haemorrhage and clotting defects in low-birthweight infants. Lancet I:545–548Google Scholar
  14. 14.
    Greenough A, Emery E, Hird MF, Gamsu HR (1993) Randomised controlled trial of albumin infusion in ill preterm infants. Eur J Pediatr 152:157–159Google Scholar
  15. 15.
    Gupta JM, Starr H, Fincher P, Lam-Po-Tang PRLC (1976) Intraventricular haemorrhage in the Newborn. Med J Aust 2:338–340Google Scholar
  16. 16.
    Hambleton G, Appleyard WJ (1973) Controlled trial of fresh frozen plasma in asphyxiated low birthweight infants. Arch Dis Child 48:31–35Google Scholar
  17. 17.
    Horbar JD (1992) Prevention of periventricular-intraventricular haemorrhage, In: Sinclair JC, Bracken MB (eds) Effective care of the newborn infant. Chapter 25 Oxford University Press, Oxford, pp 562–589Google Scholar
  18. 18.
    Johnson CA, Snyder MS, Weaver RL (1982) Effects of fresh frozen plasma infusions on coagulation screening tests in neonates. Arch Dis Chid, 57:950–952Google Scholar
  19. 19.
    Layks, Bancalari E, Malku H, Baker R, Strauss J (1980) Acute effects of albumin infusions on blood pressure and renal function in premature infants with respiratory distress syndrome. J Pediatr 97:619–623Google Scholar
  20. 20.
    Levene MI (1981) Measurement of the growth of the lateral ventricles in preterm infants with real-time ultrasound. Arch Dis Child 56:900–904Google Scholar
  21. 21.
    McClure G (1991) The use of plasma in the neonatal period. Arch Dis Child 66:373–374Google Scholar
  22. 22.
    Ment LR, Oh W, Ehrenkranz RA, Philip ASG, Vohr B, Allan W, Duncan CC, Scott DT, Taylor KJW, Katz KH, Schneider KC, Makuch RW (1994) Low dose indomethacin and prevention of intraventricular haemorrhage: a multicentre randomized trial. Pediatrics 93:543–550Google Scholar
  23. 23.
    OSIRIS Collaborative Group (1992) Early versus delayed neonatal administration of a synthetic surfactant — the judgement of OSIRIS. Lancet 340:1363–1369Google Scholar
  24. 24.
    Papile L-A, Burstein J, Burstein R, Koffler H (1978) Incidence and evolution of subependymal and intraventricular haemorrhage: a study of infants with birthweights less than 1500 gm. J Pediatr 92:529–534Google Scholar
  25. 25.
    Rennie JM (1989) Cerebral blood flow velocity variability after cardiovascular support in premature babies. Arch Dis Child 64:897–901Google Scholar
  26. 26.
    Thomas DB, Burnard ED (1973) Prevention of intraventricular haemorrhage in babies receiving artificial ventilation. Med J Aust 1:933–936Google Scholar
  27. 27.
    Tin W, Hey E, Elbourne D, Krog J (1993) An EC trial of prophylactic volume expansion in babies born more than 8 weeks early (Abstract). British Paediatric Association 65th Annual Meeting, University of Warwick, 20–23 April 1993, p 28Google Scholar
  28. 28.
    Turner T, Prowse CV, Prescott RJ, Cash JD (1981) A clinical trial on the early detection and correction of haemostatic defects in selected highrisk neonates. Br J Haematol 47:65–75Google Scholar
  29. 29.
    Waltl H, Födisch HJ, Kurz R, Hohenauer L, Mitterstieler G, Rössler H (1973) Intracranial haemorrhage in low-birth-weight infants and prophylactic administration of coagulationfactor concentrate. Lancet I:1284–1286Google Scholar
  30. 30.
    Wariyar U, Richmond S, Hey E (1989) Pregnancy outcome at 24–31 weeks gestation: mortality. Arch Dis Child 64:670–677Google Scholar
  31. 31.
    Wariyar U, Richmond S, Hey E (1989) Pregnancy outcome at 24–31 weeks gestation: neonatal survivors. Arch Dis Child 64:678–686Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • The Northern Neonatal Nursing Initiative [NNNI] Trial Group
  • D. Elbourne
    • 1
  1. 1.Perinatal Trials Service, National Perinatal Epidemiology UnitRadcliffe InfirmaryOxfordUK

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