Intravenous indomethacin for preventing mortality and morbidity in very low birth weight infants. 2000

P W Fowlie
Child Health, University of Dundee, Ninewells Hospital and Medical School, Dundee, Tayside, UK, DD1 9SY.

BACKGROUND This section is under preparation and will be included in the next issue. OBJECTIVE Indomethacin is used to treat symptomatic patent ductus arteriosus and may prevent or limit intraventricular haemorrhage in the neonatal period. This review examines the effectiveness of prophylactic intravenous indomethacin in reducing the mortality and morbidity associated with these conditions in infants weighing less than 1750 grams at birth. METHODS A literature search from January 1980 to October 1994 was made in three computerised data bases: Medline; Embase; and the Oxford Database of Perinatal Trials. The search was updated in February 1997. METHODS Strict selection criteria were applied to clinical trials: the population had to be newborn infants of birth weight < 1751 grams; the intervention had to be prophylactic intravenous indomethacin; the trial had to be randomised and controlled; and at least one of several prespecified outcomes had to be reported in the results. METHODS The methodological quality of each study was assessed using explicit criteria. Data on relevant outcome measures were extracted on two separate occasions and, where appropriate, the results of individual trials were combined using meta-analysis techniques to provide a pooled estimate of effect. RESULTS There is a trend towards reduced neonatal mortality in infants receiving prophylactic indomethacin, pooled relative risk (RR) = 0. 85 [95% CI 0.66 to 1.09]. The incidence of symptomatic patent ductus arteriosus is significantly reduced in treated infants, pooled RR = 0.35 [0.26 to 0.47] but there is no evidence that treatment affects respiratory outcomes. Prophylactic indomethacin significantly reduces the incidence of Grade 3 and 4 intraventricular haemorrhage in treated infants, pooled RR = 0.60 [0.43 to 0.83]. There is no evidence to suggest prophylactic indomethacin is associated with any long term adverse effect although there is a trend in treated infants towards an increased incidence of necrotizing enterocolitis, and some evidence that treatment may transiently impair renal function. There is no evidence that haemostasis is disturbed. CONCLUSIONS Prophylactic treatment with indomethacin has a number of immediate benefits, in particular a reduction in symptomatic patent ductus arteriosus and severe intraventricular haemorrhage. There is no evidence at present of long-term harm. Further trials are needed to assess more precisely the effects, both beneficial and harmful, on short and long-term outcomes.

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007235 Infant, Premature, Diseases Diseases that occur in PREMATURE INFANTS.
D002317 Cardiovascular Agents Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume. Cardioactive Agent,Cardioactive Drug,Cardiovascular Agent,Cardiovascular Drug,Cardioactive Agents,Cardioactive Drugs,Cardiovascular Drugs,Agent, Cardioactive,Agent, Cardiovascular,Drug, Cardioactive,Drug, Cardiovascular
D002543 Cerebral Hemorrhage Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA. Brain Hemorrhage, Cerebral,Cerebral Parenchymal Hemorrhage,Hemorrhage, Cerebral,Intracerebral Hemorrhage,Hemorrhage, Cerebrum,Brain Hemorrhages, Cerebral,Cerebral Brain Hemorrhage,Cerebral Brain Hemorrhages,Cerebral Hemorrhages,Cerebral Parenchymal Hemorrhages,Cerebrum Hemorrhage,Cerebrum Hemorrhages,Hemorrhage, Cerebral Brain,Hemorrhage, Cerebral Parenchymal,Hemorrhage, Intracerebral,Hemorrhages, Cerebral,Hemorrhages, Cerebral Brain,Hemorrhages, Cerebral Parenchymal,Hemorrhages, Cerebrum,Hemorrhages, Intracerebral,Intracerebral Hemorrhages,Parenchymal Hemorrhage, Cerebral,Parenchymal Hemorrhages, Cerebral
D004374 Ductus Arteriosus, Patent A congenital heart defect characterized by the persistent opening of fetal DUCTUS ARTERIOSUS that connects the PULMONARY ARTERY to the descending aorta (AORTA, DESCENDING) allowing unoxygenated blood to bypass the lung and flow to the PLACENTA. Normally, the ductus is closed shortly after birth. Patent Ductus Arteriosus Familial,Patency of the Ductus Arteriosus,Patent Ductus Arteriosus
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016032 Randomized Controlled Trials as Topic Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical
D019102 Infant, Very Low Birth Weight An infant whose weight at birth is less than 1500 grams (3.3 lbs), regardless of gestational age. Very Low Birth Weight,Very-Low-Birth-Weight Infant,Infant, Very-Low-Birth-Weight,Infants, Very-Low-Birth-Weight,Very Low Birth Weight Infant,Very-Low-Birth-Weight Infants

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