MATERNAL AND EARLY CHILD HEALTH

Health Evidence Bulletins - Wales

Date of Completion: 9.1.98

The contents of this bulletin are likely to be valid for approximately one year, by which time significantly new research evidence may become available


21. Prevention of neurological handicap

(Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation)

Factors predicting a high risk of subsequent neurological handicap include: prematurity, perinatal asphyxia, haemorrhagic disease of the newborn, congenital anomalies and infections. The major determinants of neurological handicap in preterm survivors are intraventricular haemorrhage (IVH) (the incidence may be as high as 40% in very low birth-weight infants(i)) and cerebral ischaemia/atrophy. The aetiology is multifactorial but is associated with fetal distress and labour problems, and postnatal factors such as seizures, hypothermia and respiratory distress syndrome and its complications (see Chapter 20 ‘neonatal respiratory support’).
Efforts to prevent preterm labour, the importance of transfer to an appropriate unit for specialized neonatal care, antenatal steroids and optimum resuscitation are discussed in Chapter 13 ‘premature labour’ and Chapter 19 ‘care of the low birth weight baby’. Management must include sustained neurodevelopment follow up of all at risk infants.
Much of the evidence relating to the reduction of neurological handicap in the pre-term infant is related to short term outcome measures such as improved appearance on cerebral ultrasound. Data on long-term clinical benefit are relatively scanty(i, ii).
i. Wells JT, Ment LR. Prevention of intraventricular hemorrhage in preterm infants. Early Human Development. 1995; 42: 209-223. (Type I evidence - systematic review);
ii. Internal Review Group. (Type V evidence - expert opinion See Contributors)
21.1 ALL INFANTS  
The Statements The Evidence
21.1a. Administration of Vitamin K (1mg intramuscular) to the infant is currently an effective way of reducing the incidence of haemorrhagic disease of the newborn, of which, intracranial haemorrhage is one of the most important manifestations(i).
(Health gain notation - 2 "likely to be beneficial")

caveat: Reports of an association between intramuscular Vitamin K and childhood cancer(ii) have not been substantiated(i, iii). While there is no question that Vitamin K is an important treatment for those babies at highest risk of haemorrhagic disease, further trials of the value of Vitamin K in low risk children should be encouraged.

i. Brousson MA, Klein MC. Controversies surrounding the administration of Vitamin K to newborns: a review' Canadian Medical Association Journal. 1996; 154: 307-315
(Type I evidence - systematic review);
ii. Golding J, Greenwood R, Birmingham K, Mott M. Childhood Cancer, intramuscular Vitamin K, and pethidine given during labour British Medical Journal 1992; 305: 341-346
(Type IV evidence - case note study of 195 children with cancer);
iii. Klebanoff MA, Read JS, Mills JL, Shiono PH. The risk of childhood cancer after neonatal exposure to vitamin K. New England Journal of Medicine. 1993; 329(13): 905-908
(Type IV evidence - case control study of 48 children with cancer each matched with 5 randomly selected controls)
21.1b. Current professional recommendations remain(i):
(Health gain notation - 1 "beneficial").
  • Vitamin K is given by mouth to all infants on the day of birth (500m g konakion as a single dose or 2 doses of 250m g)
  • Infants who are breast fed are given further doses of vitamin k at daily (50m g) or weekly (200m g) doses for 26 weeks; or at the 7-10 day (500m g) and 4-6 week (500m g) check.
  • If the oral route is not available or thought to be unreliable, that vitamin K is given by intramuscular injection (100m g).

Oral regimens avoid the trauma of injection, the potential risk of high blood concentrations (and the unsubstantiated risk of cancer - see statement a). However, the efficacy of multiple oral doses is not well established and the only licensed oral preparation is a multidose glass ampoule(i, ii). Further recommendations from the Department of Health are due early in 1998(iii).

i. British Paediatric Association. Vitamin K prophylaxis in infancy. London: British Paediatric Association, 25 August 1992.
(Type V evidence - expert opinion);
ii. Barton JS, Tripp JH, McNinch AW. Neonatal vitamin K prophylaxis in the British Isles: Current practice and trends. British Medical Journal. 1995; 310: 632-633.
http://www.bmj.com/cgi/content/full/310/6980/632
(Type IV evidence - questionnaire to neonatal units - 98% response rate);
iii. As a letter from the Chief Medical and Nursing Officers; Personal communication, Department of Health.

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21.1c. Ultrasound is effective in the diagnosis of intraventricular haemorrhage (i).
(Health gain notation - 1 "beneficial")
i. Koppe JG. Prevention of brain haemorrhage and ischaemic injury in premature babies. Lancet. 1996; 348: 208-209
(Type V evidence - expert commentary)
21.2 The PRETERM INFANT  
The Statements The Evidence
21.2a. The prophylactic administration of Indomethacin to the preterm infant significantly reduces the incidence of intraventricular haemorrhage (8% with grades 3 or 4 IVH versus 13% in the control group) and symptomatic patent ductus arteriosus in infants weighing less than 1750g at birth(i) and does not result in adverse cognitive or motor outcomes at 36 months corrected age of very low birthweight infants (600-1250g)(ii).

(Health gain notation - 3 "trade-off between beneficial and adverse effects")

caveat: An increased risk of impaired renal function and necrotizing enterocolitis has been reported(i, iii).

i. Fowlie PW. Prophylactic indomethacin: systematic review and meta-analysis. Archives of Disease in Childhood. 1996; 74(2): F81-F87
(Type I evidence - systematic review and meta-analysis);
ii. Ment LA, Vohr B, Oh W et al. Neurodevelopmental outcome at 36 months’ corrected age of preterm infants in the multicenter indomethacin intraventricular hemorrhage prevention trial. Pediatrics. 1996; 98(4): 714-718
(Type III evidence - randomised prospective trial of 431 neonates);
iii. Grosfeld JL, Chaet M, Molinari F et al. Increased risk of necrotizing enterocolitis in premature infants with patent ductus arteriosus treated with indomethacin. Annals of Surgery. 1996; 224(3): 350-355
(Type III evidence - case study of 252 infants compared with 764 matched controls)

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21.2b. Vitamin E was initially recommended in the prevention of retinopathy of prematurity although a review of 9 randomised trials did not reveal a statistically significant reduction (i). However, in the same group, a small reduction in some forms of intraventricular haemorrhage was found. The clinical value of this reduction has been questioned and further studies are needed, concerning both its value in reducing neurological handicap and retinopathy of prematurity (ii).
(Health gain notation - 4 "unknown")
ii. Law MR, Wijewardene K, Wald NJ. Is routine vitamin E administration justified in very low birthweight infants? Developmental Medicine and Child Neurology. 1990; 32: 442-450
(Type I evidence - systematic review)
i. Wells JT, Ment LR. Prevention of intraventricular hemorrhage in preterm infants (p.222) Early Human Development. 1995; 42: 209-233
(Type I evidence - systematic review)
21.2c. There is no evidence that the routine early use of fresh frozen plasma (as a plasma expander in infants of gestational age <32 weeks) is effective in reducing the risk of neurological handicap(i).
(Health gain notation - 5 "unlikely to be beneficial")
i. Northern Neonatal Nursing Initiative Trial Group 'Randomized trial of prophylactic early fresh-frozen plasma or gelatin or glucose in preterm babies: outcome at 2 years Lancet 1996; 348: 229-232
(Type II evidence - randomised controlled trial of 776 babies)
21.2d. Trials of antenatal administration of phenobarbital have shown a minimal reduction in the incidence of intraventricular haemorrhage with an increase in the incidence of respiratory distress and a requirement for ventilation(i, ii, iii).

(Health gain notation - 5 "unlikely to be beneficial")

i. Horbar JD. Prevention of periventricular-intraventricular hemorrhage. In: Effective care of the newborn infant. Editors. J Sinclair and MB Bracken. Oxford: Oxford University Press, 1992 pp.565-566
(Type I evidence - systematic review);
ii. Doyle L. Antenatal phenobarbitone and neonatal outcome. Lancet 1996; 348: 975-6
(Type I evidence - review including a meta-analysis and several trials)
21.2e. The administration of phenobarbital to the newborn has shown no significant decrease in the incidence of intraventricular haemorrhage(i).

(Health gain notation - 5. "unlikely to be beneficial")

i. Horbar JD. Prevention of periventricular-intraventricular hemorrhage. In: Effective care of the newborn infant. Editors. J Sinclair and MBBracken. Oxford: Oxford University Press, 1992 pp. 566-568
(Type I evidence - systematic review)
21.2f. Sodium ethamsylate is widely used to reduce capillary bleeding in surgery. A small reduction of the overall incidence of intraventricular haemorrhage has been demonstrated associated with a non-significant improvement of neurological outcome in the treated group(i, ii).

(Health gain notation - 2 "likely to be beneficial")

i. Wells JT, Ment LR. Prevention of intraventricular hemorrhage in preterm infants Early Human Development. 1995; 42: 209-233
(Type I evidence - systematic review)

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21.2g. Antenatal steroids have a significant effect in reducing the incidence of respiratory distress syndrome (RDS) and, in addition, have been shown to be associated with a reduced incidence of intraventricular haemorrhage (OR 0.49)(i). This finding may be related to the reduction of RDS or a direct effect of steroids on the central nervous system(i). (Health gain notation - 3 "trade-off between beneficial and adverse effects")
caveat: A greater incidence of necrotizing enterocolitis was observed in several studies(i).
i. Wells JT, Ment LR. Prevention of intraventricular hemorrhage in preterm infants Early Human Development. 1995; 42: 209-233

(Type I evidence - systematic review)

21.2h. Surfactant, while known to be effective in the treatment of respiratory distress syndrome, has no significant effect in reducing the incidence of intraventricular haemorrhage (i).
(Health gain notation -5 "unlikely to be beneficial")

caveat: Its combined use with steroids may have benefits(i).
(Health gain notation - 4 "unknown")

i. Wells JT, Ment LR. Prevention of intraventricular hemorrhage in preterm infants Early Human Development. 1995; 42: 209-233

(Type I evidence - systematic review)

21.2i. Observational study suggests that in utero exposure to magnesium sulphate is associated with a lower prevalence of cerebral palsy in infants weighing < 1500g. In view of the anticipated widespread adoption of magnesium sulphate in the management of fulminating pregnancy induced hypertension, further evidence should become available(i).
(Health gain notation - 4 "unknown")
i. Nelson KB, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? Pediatrics. 1995: 95(2): 263-269

(Type IV evidence - observational study of 636 children)

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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk