RESUMO
We enrolled 61 neonates of 600 to 1250 gm birth weight with evidence of low-grade intraventricular hemorrhage at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that indomethacin (0.1 mg/kg given intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would prevent extension of intraventricular hemorrhage. Twenty-seven infants were assigned to receive indomethacin; 34 infants received saline placebo. There were no significant differences between the two groups in birth weight, gestational age, sex, Apgar scores, percentage of infants treated with surfactant, or distribution of hemorrhages at the time of the first cranial sonogram (echo-encephalogram). Within the first 5 days, 9 of 27 indomethacin-treated and 12 of 34 saline solution-treated infants had extension of their initial intraventricular hemorrhage (p = 1.00). Four indomethacin-treated and three saline solution-treated infants had parenchymal extension of the hemorrhage. Indomethacin was associated with closure of a patent ductus arteriosus by the fifth day of life (p = 0.003). There were no differences in adverse events attributed to indomethacin. We conclude that in very low birth weight infants with low grade intraventricular hemorrhage within the first 6 postnatal hours, prophylactic indomethacin therapy promotes closure of the patent ductus arteriosus and is not associated with adverse events, but does not affect the cascade of events leading to parenchymal involvement of intracranial hemorrhage.
Assuntos
Hemorragia Cerebral/tratamento farmacológico , Indometacina/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Esquema de Medicação , Permeabilidade do Canal Arterial/tratamento farmacológico , Feminino , Humanos , Indometacina/administração & dosagem , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
Because earlier studies suggested that preterm infants with germinal matrix hemorrhage or intraventricular hemorrhage or both (GMH/IVH) present within the first 12 postnatal hours are at greatest risk for the development of high-grade hemorrhage and neurodevelopmental disability, we examined the risk factors for this insult among 229 neonates of 600 to 1250 gm birth weight in a multicenter study. All had echoencephalography (ECHO) within the first 11 hours and serially for the next 20 days; risk factor data were collected prospectively. Forty-three infants had GMH/IVH within the first 5 to 11 hours (mean age at ECHO 7.7 hours): 18 GMH and 21 grade II, 1 grade III, and 3 grade IV IVH. One hundred eighty-six infants did not have GMH/IVH at a mean age of 7.9 hours. Both groups of infants were similar in birth weight, gestational age, maternal risk factors, cord pH values, and surfactant therapy before ECHO. The group with early IVH had more vertex presentations than the group without early IVH (79% vs 55%, p = 0.043), less maternal tocolytic use (42% vs 60%, p = 0.029), and more vaginal deliveries (67% vs 44%, p = 0.005). In the first 21 days, severe IVH developed in 12 infants with early IVH and in 6 infants without early IVH (p < 0.001). There were more neonatal deaths (16% vs 6%, p = 0.035) and more deaths at any time during the primary hospitalization (23% vs 9%, p = 0.010) among the early IVH group than among the group without early IVH. Multivariate analysis indicated that the mode of delivery, fetal presentation, and birth weight were important and independent prognostic indicators of IVH.
Assuntos
Hemorragia Cerebral/etiologia , Recém-Nascido de Baixo Peso , Peso ao Nascer , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/mortalidade , Ventrículos Cerebrais , Ecoencefalografia , Feminino , Humanos , Recém-Nascido , Apresentação no Trabalho de Parto , Masculino , Gravidez , Complicações na Gravidez , Fatores de RiscoRESUMO
We admitted 36 preterm neonates (600 to 1250 gm birth weight) with normal 6-hour echoencephalograms to a randomized, placebo-controlled prospective trial to determine whether a low dose of indomethacin would prevent germinal matrix or intraventricular hemorrhage and permit adequate urinary output. Between the sixth and tenth postnatal hours, indomethacin (0.1 mg/kg) or placebo was administered intravenously every 24 hours for a total of three 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, serum indomethacin levels, and renal and clotting functions were monitored. No differences in birth weight, gestational age, or Apgar scores were noted between the two groups of infants. Two indomethacin-treated infants and three infants given placebo had significant urinary output difficulties, requiring that the study medication be withheld. Of 19 infants given indomethacin, two had germinal matrix or intraventricular hemorrhage, in comparison with 8 of 17 infants given saline solution (p = 0.02). Of the infants who had a left-to-right patent ductus arteriosus shunt before treatment, 64% of the indomethacin-treated and 33% of the saline solution-treated infants no longer had a patent ductus arteriosus on day 5. Ductal status appeared unrelated to the development of germinal matrix or intraventricular hemorrhage.
Assuntos
Hemorragia Cerebral/prevenção & controle , Indometacina/uso terapêutico , Recém-Nascido de Baixo Peso , Hemorragia Cerebral/complicações , Permeabilidade do Canal Arterial/complicações , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Doenças Urológicas/complicaçõesRESUMO
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 five 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 against neonatal intraventricular hemorrhage by acting on the cerebral microvasculature.
Assuntos
Hemorragia Cerebral/prevenção & controle , Indometacina/uso terapêutico , Recém-Nascido de Baixo Peso , Doenças do Prematuro/prevenção & controle , 6-Cetoprostaglandina F1 alfa/sangue , Hemorragia Cerebral/sangue , Ensaios Clínicos como Assunto , Permeabilidade do Canal Arterial/diagnóstico , Permeabilidade do Canal Arterial/prevenção & controle , Ecocardiografia , Humanos , Recém-Nascido , Doenças do Prematuro/sangue , Estudos Prospectivos , Distribuição Aleatória , Tromboxano B2/sangueRESUMO
Serial cranial ultrasound studies, 133xenon inhalation cerebral blood flow determinations, and risk factor analyses were performed in 31 preterm neonates. Contrast echocardiographic studies were additionally performed in 16 of these 31 infants. Sixty-one percent were found to have germinal matrix or intraventricular hemorrhage. Seventy-four percent of all hemorrhages were detected by the thirtieth postnatal hour. The patients were divided into three groups: early GMH/IVH by the sixth postnatal hour (eight infants) interval GMH/IVH from 6 hours through 5 days (10), and no GMH/IVH (12). Cerebral blood flow values at 6 postnatal hours were significantly lower for the early GMH/IVH group than for the no GMH/IVH group (P less than 0.01). Progression of GMH/IVH was observed only in those infants with early hemorrhage, and these infants had a significantly higher incidence of neonatal mortality. Ventriculomegaly as determined by ultrasound studies was noted equally in infants with and without GMH/IVH (50%) and was not found to correlate with low cerebral blood flow. The patients with early hemorrhage were distinguishable by their need for more vigorous resuscitation at the time of birth and significantly higher ventilator settings during the first 36 postnatal hours, during which time they also had higher values of PCO2. An equal incidence of patent ductus arteriosus was found across all of the groups. We propose that early GMH/IVH may be related to perinatal events and that the significant decrease in cerebral blood flow found in infants with early GMH/IVH is secondary to the presence of the hemorrhage itself. Progression of early GMH/IVH and new interval GMH/IVH may be related to later neonatal events known to alter cerebral blood flow.