{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:38:43Z","timestamp":1789663123982,"version":"4.0.1"},"reference-count":32,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,9,1]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>Posthemorrhagic ventricular dilation (PHVD) is a complication of intraventricular hemorrhage in preterm infants and is associated with a high risk of long-term disability. Furosemide and acetazolamide are used widely in the treatment of PHVD in the hope of avoiding the need for placement of a ventriculoperitoneal shunt, but these drugs have not been evaluated in a controlled trial. This article reports a multicenter, randomized, controlled trial designed to test the hypothesis that these drugs would reduce the rate of shunt placement (or death) and increase survival to 1 year of age without disability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Between 1992 and 1996, 177 infants who were less than 3 months past term and had ventricular width &amp;gt;4 mm above the 97th centile following intraventricular hemorrhage were assigned randomly to either standard therapy or standard therapy plus drug therapy with acetazolamide (100 mg\/kg\/d) plus furosemide (1 mg\/kg\/d). Infants who were enrolled in the trial had a median gestational age of 28.6 weeks and were enrolled at a mean postnatal age of 3.6 weeks. Forty-four percent were reported to have a cerebral parenchymal lesion on ultrasound scan at randomization. The primary outcome measure of death or shunt placement (known in all but 1 infant) occurred in 56 of 88 infants who were allocated to drug plus standard therapy compared with 46 of 88 who were allocated to standard therapy. The risk ratio was 1.23 (95% confidence interval: 0.95\u20131.59). Neurodevelopmental outcome information at a corrected age of 1 year (known in all but 3 of 149 surviving infants) included disability or neuromotor impairment in 54 of 67 infants (81%) who were allocated to drug plus standard therapy and 52 of 69 infants (66%) who were allocated to standard therapy. Seventy-two of 85 infants (85%) who were allocated to drug therapy either died or were disabled or impaired at 1 year compared with 62 of 89 infants (70%) who were treated with standard therapy (risk ratio: 1.22; 95% confidence interval: 1.03\u20131.4376). The excess risk of these adverse outcomes was greater among infants who did not have a cerebral parenchymal lesion seen on ultrasound examination at trial entry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions.<\/jats:title><jats:p>These results suggest that the use of acetazolamide and furosemide in preterm infants with PHVD is ineffective in decreasing the rate of shunt placement and is associated with increased neurologic morbidity. This treatment therefore cannot be recommended.<\/jats:p><\/jats:sec>","DOI":"10.1542\/peds.108.3.597","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:55:51Z","timestamp":1092441351000},"page":"597-607","source":"Crossref","is-referenced-by-count":136,"title":["Randomized, Controlled Trial of Acetazolamide and Furosemide in Posthemorrhagic Ventricular Dilation in Infancy: Follow-Up at 1 Year"],"prefix":"10.1542","volume":"108","author":[{"given":"Colin R.","family":"Kennedy","sequence":"first","affiliation":[{"name":"From the Department of Pediatric Neurology, Southampton General Hospital, Southampton;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ayers","sequence":"additional","affiliation":[{"name":"National Perinatal Epidemiology Unit, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Institute of Primary Care and General Practice, Sheffield University, Sheffield;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Elbourne","sequence":"additional","affiliation":[{"name":"Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London;"},{"name":"National Perinatal Epidemiology Unit, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hope","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, John Radcliffe Hospital, Oxford; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Johnson","sequence":"additional","affiliation":[{"name":"National Perinatal Epidemiology Unit, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of The International PHVD Drug Trial Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2001,9,1]]},"reference":[{"key":"2021121009593139500_B1"},{"key":"2021121009593139500_B2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.2307\/1602514","article-title":"Long term developmental outcomes of low birthweight infants.","volume":"5","author":"Hack","year":"1995","journal-title":"Future Child"},{"key":"2021121009593139500_B3","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1651-2227.1998.tb01465.x","article-title":"Infantile hydrocephalus: declining prevalence in preterm infants.","volume":"87","author":"Fernell","year":"1998","journal-title":"Acta Paediatr Scand"},{"key":"2021121009593139500_B4","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S0022-3476(94)70023-0","article-title":"Current gestational age-related incidence of major intraventricular hemorrhage.","volume":"125","author":"Batton","year":"1994","journal-title":"J Pediatr"},{"key":"2021121009593139500_B5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1177\/088307389801300604","article-title":"Trends in the incidence and severity of intraventricular haemorrhage.","volume":"13","author":"Sheth","year":"1998","journal-title":"J Child Neurol"},{"key":"2021121009593139500_B6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/adc.65.1_Spec_No.3","article-title":"Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation.","volume":"65","author":"Ventriculomegaly Trial Group","year":"1990","journal-title":"Arch Dis Child"},{"key":"2021121009593139500_B7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1136\/fn.70.2.F129","article-title":"Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation: results at 30 months.","volume":"70","author":"Ventriculomegaly Trial Group","year":"1994","journal-title":"Arch Dis Child"},{"key":"2021121009593139500_B8"},{"key":"2021121009593139500_B9","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000028693","article-title":"Neuroendoscopic third ventriculostomy in patients less than one year old.","volume":"29","author":"Buxton","year":"1998","journal-title":"Pediatr Neurosurg"},{"key":"2021121009593139500_B10","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S0022-3476(80)80495-1","article-title":"Failure of daily lumbar punctures to prevent the development of hydrocephalus following intraventricular hemorrhage.","volume":"97","author":"Mantovani","year":"1980","journal-title":"J Pediatr"},{"key":"2021121009593139500_B11","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/S0022-3476(85)80532-1","article-title":"Serial lumbar punctures in prevention of posthemorrhagic hydrocephalus in preterm infants.","volume":"107","author":"Anwar","year":"1985","journal-title":"J Pediatr"},{"key":"2021121009593139500_B12","doi-asserted-by":"crossref","first-page":"F20","DOI":"10.1136\/fn.75.1.F20","article-title":"Phase 1 study of intraventricular recombinant tissue plasminogen activator for treatment of posthaemorrhagic hydrocephalus.","volume":"75","author":"Whitelaw","year":"1996","journal-title":"Arch Dis Child"},{"key":"2021121009593139500_B13","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1469-8749.1972.tb09774.x","article-title":"Medical management of hydrocephalus.","volume":"14","author":"Hayden","year":"1972","journal-title":"Dev Med Child Neurol"},{"key":"2021121009593139500_B14","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/j.1469-8749.1983.tb13797.x","article-title":"Isosorbide in the management of infantile hydrocephalus.","volume":"25","author":"Lorber","year":"1983","journal-title":"Dev Med Child Neurol"},{"key":"2021121009593139500_B15","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1469-8749.1992.tb14981.x","article-title":"Isosorbide in the medical management of hydrocephalus in children with myelodysplasia.","volume":"34","author":"Liptak","year":"1992","journal-title":"Dev Med Child Neurol"},{"key":"2021121009593139500_B16"},{"key":"2021121009593139500_B17","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S0022-3476(65)80087-7","article-title":"Treatment of hydrocephalus with acetazolamide.","volume":"66","author":"Huttenlocher","year":"1965","journal-title":"Pediatrics"},{"key":"2021121009593139500_B18","first-page":"189","article-title":"Medical management of hydrocephalus with acetazolamide and frusemide.","volume":"4","author":"Bergman","year":"1978","journal-title":"Ann Neurol"},{"key":"2021121009593139500_B19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0022-3476(85)80609-0","article-title":"Management of hydrocephalus in infancy: use of acetazolamide and furosemide to avoid cerebrospinal fluid shunts.","volume":"107","author":"Shinnar","year":"1985","journal-title":"Pediatrics"},{"key":"2021121009593139500_B20","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0140-6736(97)12390-X","article-title":"International randomised controlled trial of acetazolamide and furosemide in posthaemorrhagic ventricular dilatation in infancy.","volume":"352","author":"International","year":"1998","journal-title":"Lancet"},{"key":"2021121009593139500_B21","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1136\/adc.56.12.900","article-title":"Measurement of the growth of the lateral ventricles in preterm infants with realtime ultrasound.","volume":"56","author":"Levene","year":"1981","journal-title":"Arch Dis Child"},{"key":"2021121009593139500_B22"},{"key":"2021121009593139500_B23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2466\/pms.1994.79.1.203","article-title":"Comparison of Vineland Adaptive Behaviour Scales\u2014survey form age equivalent and standard score with the Bayley Mental Development Index.","volume":"79","author":"Raggio","year":"1994","journal-title":"Percept Mot Skills"},{"key":"2021121009593139500_B24","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/S0140-6736(98)00379-1","article-title":"Trials stopped early: too good to be true?","volume":"535","author":"Pocock","year":"1999","journal-title":"Lancet"},{"key":"2021121009593139500_B25","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1016\/S0140-6736(98)00060-9","article-title":"Acetazolamide in posthaemorrhagic ventricular dilatation.","volume":"352","author":"Raupp","year":"1998","journal-title":"Lancet"},{"key":"2021121009593139500_B26","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1651-2227.1991.tb11724.x","article-title":"Acute effects of acetazolamide on cerebral blood flow velocity and pCO2 in the newborn infant.","volume":"80","author":"Cowan","year":"1991","journal-title":"Acta Paediatr Scand"},{"key":"2021121009593139500_B27","doi-asserted-by":"crossref","first-page":"F123","DOI":"10.1136\/fn.70.2.F123","article-title":"Infantile hydrocephalus epidemiology: an indicator of enhanced survival.","volume":"70","author":"Fernell","year":"1994","journal-title":"Arch Dis Child"},{"key":"2021121009593139500_B28","doi-asserted-by":"crossref","first-page":"F169","DOI":"10.1136\/fn.75.3.F169","article-title":"The changing epidemiology of cerebral palsy.","volume":"75","author":"Pharoah","year":"1996","journal-title":"Arch Dis Child"},{"key":"2021121009593139500_B29","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1542\/peds.84.5.797","article-title":"Intraventricular hemorrhage in preterm infants: declining incidence in the 1980s.","volume":"84","author":"Philip","year":"1989","journal-title":"Pediatrics."},{"key":"2021121009593139500_B30","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/j.1651-2227.1997.tb15186.x","article-title":"Cerebrospinal fluid plasminogen activator inhibitor-1: a prognostic factor in posthaemorrhagic hydrocephalus.","volume":"86","author":"Hansen","year":"1997","journal-title":"Acta Paediatr"},{"key":"2021121009593139500_B31","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1227\/00006123-198610000-00010","article-title":"Lysis of intraventricular clot with urokinase in an animal model. Part 3. Effects of intraventricular urokinase on clot lysis and posthaemorrhagic hydrocephalus.","volume":"19","author":"Pang","year":"1986","journal-title":"Neurosurgery."},{"key":"2021121009593139500_B32","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1227\/00006123-199208000-00016","article-title":"Subacute hydrocephalus after experimental subarachnoid haemorrhage: its prevention by intrathecal fibrinolysis with recombinant tissue plasminogen activator.","volume":"31","author":"Brinker","year":"1992","journal-title":"Neurosurgery"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/108\/3\/597\/888714\/597.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/108\/3\/597\/888714\/597.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T07:34:57Z","timestamp":1734507297000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/108\/3\/597\/66534\/Randomized-Controlled-Trial-of-Acetazolamide-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9,1]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2001,9,1]]},"published-print":{"date-parts":[[2001,9,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.108.3.597","relation":{},"ISSN":["1098-4275","0031-4005"],"issn-type":[{"value":"1098-4275","type":"electronic"},{"value":"0031-4005","type":"print"}],"subject":[],"published":{"date-parts":[[2001,9,1]]}}}