Randomized indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight infants

doi:10.1016/S0022-3476(85)80197-9

The Journal of Pediatrics

Volume 107, Issue 6, December 1985, Pages 937-943

https://doi.org/10.1016/S0022-3476(85)80197-9 Get rights and content

We admitted 48 preterm neonates (600 to 1250 gm birth weight, normal 6-hour, echoencephalograms) to a randomized prospective indomethacin or placebo trial for the prevention of neonatal intraventricular hemorrhage. Beginning at 6 postnatal hours, indomethacin or placebo was administered intravenously every 12 hours for a total of fie doses. Cardiac ultrasound studies to assess the status of the ductus arteriosus were performed at 6 postnatal hours and on day 5. Urinary output, serum electrolytes, and renal and clotting functions were monitored. No differences in birth weight, gestational age, Apgar scores, or ventilatory needs were noted between the two groups. Six infants given indomethacin had intraventricular hemorrhage, compared to 14 control infants (P=0.02). The indomethacin-treated group had significant decreases in serum prostaglandin values 30 hours after the initiation of therapy. The overall incidence of patent ductus arteriosus was 82% at 6 postnatal hours; 84% of the indomethacin-treated infants experienced closure of the ductus, compared to 60% of the placebo-treated patients. Closure of the ductus was not related to incidence of intraventricular hemorrhage. We speculate that indomethacin may provide some protection aganist neonatal intraventricular hemorrhage by acting on the cerebral microvasculature.

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Citation Excerpt :
Following initial observational studies of PDA closure in 6 neonates given indomethacin,66 subsequent controlled trials showed higher PDA closure in treated neonates compared with placebo.67,68 Indomethacin also decreased the risk of IVH compared with placebo-treated neonates.68–70 Meta-analyses confirmed efficacy on ductal closure but with significant renal, gastrointestinal, hematologic, and other adverse effects.2,71

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Supported by Grant 6-366 from the March of Dimes Birth Defects Foundation, by the Charles B. Culpeper Foundation, and by Grant RR 00125 from the National Institutes of Health.

Submitted for publication April 18, 1985; accepted June 12, 1985.

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Randomized indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight infants†

Early Hum Dev

J Pediatr

J Pediatr

J Pediatr

J Pediatr

Lancet

Lancet

J Pediatr

J Pediatr

J Pediatr

Lancet

J Pediatr

J Pediatr

Prostaglandins

Diagnosis and follow-up of intraventricular and intracerebral hemorrhages by ultrasound studies of infant's brains through the fontanelles and sutures

Pediatrics

Intraventricular hemorrhage in the high-risk preterm infant: incidence and outcome

Ann Neurol

Intraventricular hemorrhage: a prospective evaluation of etiopathogenesis

Pediatrics

Prediction of death and major handicap in very preterm infants by brain ultrasound

Lancet

Does phenobarbitone prevent periventricular hemorrhage in very-low-birth-weight babies? A controlled trial

Pediatrics

Beagle puppy model of intraventricular hemorrhage: randomized indomethacin prevention trial

Neurology

Protective effect of vitamin E (dll-alphatocopherol) against intraventricular haemorrhage in premature babies

Br Med J

Pharmacology and endogenous roles of prostaglandin endocrioxides, thromboxane A2 and prostacyclin

Pharmacol Rev

The role of prostaglandins in the central nervous system

Ann Rev Physiol

Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs

Nature

Clinical applications of prostaglandins and their inhibitors

Stroke

Indomethacin prevents impaired perfusion of the dog's brain after global ischemia

Stroke

Pharmacology and endogenous roles of prostaglandin endocrioxides, thromboxane A₂ and prostacyclin