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Treatment and outcome of intracranial hemorrhage
IVH grades I and II did not have a negative influence on the course of the infants development. The hemorrhage was resolved without dilation of the ventricles and the children show a development equally favourable to that of preterm neonates without hemorrhage. Poorest outcome is related to grade III. But the number of such cases in our investigation is small. The two babies, having survived IVH grade III, developed a posthemorrhagic hydrocephalus. These results differ from those of Fitzhardinge et al. [4], who could demonstrate a higher percentage of handicapped children both in former preterm neonates with IVH grades I and II and in preterm neonates without hemorrhage. This difference may be caused by the greater number of preterm infants with birthweights below 1000 g in Fitzhardinge’s study. The children under 1000 g examined by Williamson et al. [5] did not show any correlation between outcome and degree of intraventricular hemorrhage either. The incidence of abnormal outcome in these children was high. On the other hand, abnormal outcome for infants with birthweights greater than 1000 g appeared to be more directly related to grade of hemorrhage than to birthweight. Williamson’s study is consistent with our own in the case of IVH grades III and IV, but differs in IVH grades I and II. We believe that many of the infants in this study with IVH grades I and II were under 1000 g, whereas in the case of those of IVH grades III and IV, weight becomes a relatively unimportant factor. In our study there are almost exclusively infants weighing over 1000 g. This could account for the divergences in the results of our two studies. In our clinic, we try to keep up-to-date: as concerns the proof of hemorrhages, we have replaced the classical CT-method with the more elegant ultrasound imaging. This fact may explain why we have only a small number of infants with intracranial hemorrhages documented by CT-scan. References 1. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage; a study of infants with birthweights less than 1,500 gm. J Pediatr 1978; 92: 529-534. 2. Kotlarek F. Computertomographische Befunde bei natalen Enzephalopathien und ihre Wertigkeit fiir die Nah- und Langzeitprognose. Habilitationsschrift, Aachen 1981. 3. Krishnamoorthy KS, Shannon DC, DeLong GR et al. Neurologic sequelae in the survivors of neonatal .intraventricular hemorrhage. Pediatrics 1979; 64: 233-237. 4. Fitzhardinge PM, Flodmark 0, Fitz CR, Ashby S. The prognostic value of computed tomography of the brain in asphyxiated premature infants. J Pediatr 1982; 100: 476-481. 5. Williamson WD, Desmond MM, Wilson GS, Andrew L, Garcia-Prats JA. Early neurodevelopmental outcome of low birthweight’ infants surviving neonatal intraventricular hemorrhage. J Perinat Med 1982; 10: 34-41.
Treatment and outcome of intracranial hemorrhage P.M. Fitzhardinge, Department of Pediatrics, Unioersity of Toronto, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario MSG 1X5, Canada Computed tomography (CT) and ultrasound (U/S) surveys of the brains of very low. birthweight infants have shown a remarkably consistent incidence of germinal layer (GLH) and intraventricular hemorrhage (IVH). Most studies report such
hemorrhages in approximately 45% of infants with birthweights less than 1500 g with the majority of bleeds occurring in those under 1000 g. Therapy in the neonatal period has concentrated on the prevention of extensive degrees of hemorrhage and the complication of hydrocephalus. Other papers at this Congress have dealt with the pathogenesis of GLH and the obstetrical and neonatal measures used to reduce the incidence of bleeding. These measures are directed towards avoidance of situations likely to produce trauma and/or hypoxic-ischemic insults to the brain both during the intrapartum and neonatal period, as well as avoidance of wide swings of cerebral blood flow and blood osmolarity during the first few days after birth. Specific treatment for the prevention of IVH has been generally disappointing. A preliminary study by Donn et al. suggested that phenobarbitone, when given prophylactically to at-risk infants, may reduce the incidence of GLH/IVH [ 11.These workers reported a 71% reduction in hemorrhage in 30 very low birthweight infants when compared with 30 matched controls. No specific mechanism of action was suggested for the phenobarbitone effect. This study has since been repeated by other investigators who have failed to confirm the prophylactic effect [2,3]. Another approach to therapy has involved a drug known to have a stabilizing action on capillary wall integrity. Morgan, in a randomized controlled study of 70 low birthweight neonates, has reported a significant reduction in the incidence of GLH in those infants treated at 2 h of age with ethamsylate [4]. However, there was no difference in incidence of major bleeds or of neonatal death between the treated and control groups. Ventricular dilatation is an accompaniment of most major IVH and is persistent in approximately 25%. A varying number of cases with persistent dilatation show a progressive increase in intracranial pressure requiring a shunt procedure for hydrocephalus. Investigators have attempted to reduce the incidence of hydrocephalus by repeated lumbar punctures commencing either at the first evidence of IVH [5] or after the onset of progressive ventricular dilatation has occurred [6]. The results of these intervention measures are difficult to interpret due to lack of controls and to the fact that, in the majority of cases, the increased intraventricular pressure is temporary and ventricular size becomes stabilized without any intervention [7]. Nevertheless, in cases of acutely raised intracranial pressure, repeated lumbar or ventricular taps or the oral administration of glycerol may be helpful as a temporary measure until a shunt procedure can be performed. The neonatal mortality associated with GLH/IVH varies directly with the extent of the hemorrhage and the degree of prematurity of the baby. During 1977-78 there was a tendency in some centers to withdraw life supports for babies with extensive hemorrhage. During those years we had only one survivor in 13 infants under 1500 g with grade IV IVH [8]. In 1979, preliminary results from follow-up encouraged us to maintain aggressive support of all babies unless persistent seizures or abnormal posturing was present. A recent study from the same unit, of babies born in 1980 who weighed less than 1250 g and whose management followed the new policy, reported that 7 of 18 babies survived a grade IV IVH [9]. Prospective studies on the outcome of low birthweight infants with documented GLH/IVH suffer from small samples and short-term follow-up. Nevertheless, the results from different centers appear to be fairly consistent. The presence, per se, of
346
blood in the germinal layer or the ventricles does not increase the risk of subsequent cerebral palsy or mental retardation. Studies suggest that grade IV hemorrhage is associated with a greater risk for later handicap but the number of such survivors is still too small for statistical analysis. Schub et al. compared a’group of 33 babies of gestational age below 35 wk with GLH t IVH with a matched control group of 30 infants and showed no -difference in incidence of major or minor sequelae between the 2 groups [lo]. In a prospective, study of 62 surviving asphyxiated babies born during 1977-78 with birthweights less than 1500 g, we were unable to show any relationship between CT findings’ during the first 2 wk and neurodevelopmental status at 2 yr post-term except for the fact that hydrocephalus occurred only in infants with preceding IVH [8]. Seventeen of the 27 with grade II or III IVH were normal at 2 yr. In a similar study from the same unit using U/S to diagnose hemorrhage in a population of appropriate for gestational age babies with birthweights less than 125 1 g, Pape et al. reported 11 of 12 children to be normal at 9 mth post-term following grade I to III IVH compared with 16 of 23 without antecedent hemorrhage 191. However, only 2 of the 7 children with grade IV were normal: 4 developed major neurological sequelae, 1 had mild developmental delay. The incidence of intracranial hemorrhage in term neonates is unknown as no systematic population scanning has been reported but it appears to be much more common than suggested by autopsy studies. Flodmark et al. reported that intracranial hemorrhage was diagnosed by CT in 91 (61%) of 148 neonates weighing more than 2500 g who were scanned because of neurological symptoms [Ill. IVH was present in 8 (5%), subdural hemorrhage in 13 (9%), and hemorrhage into brain parenchyma in 17 (12%). Mortality was highest in those with IVH or parenchymal hemorrhage (25%). Therapy in the term infant has been directed towards alleviation of acutely raised intracranial pressure (a common early complication of parenchymal and IVH) either by surgical decompression, clot removal or shunt. Except for those with isolated subarachnoid hemorrhage, the outlook for term infants with intracranial bleeding appears to be considerably worse than for the premature counterpart. In a prospective 2 yr study of 62 term infants surviving postasphyxial encephalopathy, 15 presented with blood in the ventricles and/or brain tissue [ 121. Ten of the 15 developed handicapping sequelae. All 6 with IVH presented with severe hydrocephalus or quadriplegia. All 5 children with infratentorial parenchymal hemorrhage were severely handicapped. In contrast, 3 of the 5 with supratentorial parenchymal hemorrhage appeared normal at 2 yr. The remaining two developed severe cerebral palsy. In summary, the most effective treatment for intracranial hemorrhage seems to be a perinatal approach which minimizes hypoxic-ischemic insult to the brain. Both neonatal mortality and morbidity are dependent upon the gestation age. The incidence and attendant mortality of GLH/IVH is high in the very immature infant but hemorrhage per se does not appear to influence the risk for neurodevelopmental sequelae in the survivors unless there is an associated parenchymal hemorrhagic infarction. In the full term infant, on the other hand, while intracranial hemorrhage is much less common and less likely to be fatal than in the preterm infant, it is associated with a high incidence of neurodevelopmental sequelae of a very severe and handicapping nature.
347
References I. Donn SM, Roloff DW, Goldstein GW. Prevention of intraventricular haemorrhage in preterm infants by phenobarbitone: a controlled trial. Lancet 1981; ii: 215-217. 2. Morgan MEI. Massey RF, Cooke RWI. Does phenobarbitone prevent periventricular hemorrhage in very low-birth-weight babies?: A controlled trial. Pediatrics 1982; 70: 186- 189. 3. Hope PL, Stewart AL, Thorburn RJ, et al. Failure of phenobarbitone to prevent intraventricular haemorrhage in small preterm infants. Lancet 1982; i: 444-445. 4. Morgan MEI, Benson JWT, Cooke RWI. Ethamsylate reduces the incidence of periventricular haemorrhage in very low birthweight babies. Lancet 1981; ii: 830-831. 5. Mantovani JF, Pasternak JF, Mathew OP. et al. Failure of daily lumbar punctures to prevent the development of hydrocephalus following intraventricular hemorrhage. J Pediatr 1980; 97: 278-281. 6. Papile LA, Burstein J, Burstein R, et al. Posthemorrhagic hydrocephalus in low-birth-weight infants: treatment by serial lumbar punctures. J Pediatr 1980; 97: 273-277. 7. Levene MI, Starte DR. A longitudinal study of post-haemorrhagic ventricular dilatation in the newborn. Arch Dis Child 1981; 56: 905-910. 8. Fitzhardinge PM, Flodmark 0, Fitz CR, et al. The prognostic value of computed tomography of the brain in asphyxiated premature infants. J Pediatr 1982; 100: 476-481. 9. Pape. K, Bennett-Britton S, Szymonowicz W, et al. Relationship of neonatal brain hemorrhage to death and neurodevelopmental outcome. Pediatr Res 1982; 16: 338A. 10 Schub HS, Ahmann PA, Dykes FD, et al. Prospective long-term follow-up of prematures with subependymal/intraventricular hemorrhage. Pediatr Res 198 1; 15: 7 Il. 11 Flodmark 0, Fitz CR, Harwood-Nash DC. The CT diagnosis of intracranial hemorrhage and hypoxic/ischemic brain damage in neonates. J Comput Assist Tomogr 1980; 4: 775-787. 12 Fitzhardinge PM, Flodmark 0, Fitz CR, et al. The prognostic value of computed tomography as an adjunct to assessment of the term infant with postasphyxial encephalopathy. J Pediatr 1981; 99: 771-78 1.
Diagnostic value of cardiorespirography K. Jahrig, Universitiits-Kinderklinik,
in neonatal intracranial haemorrhage
Soldtmanstr.
1.5, DDR-2200
Greifswald,
(NIH) G.D.R.
Introduction
Computerized tomographic and real-time ultrasonic scanning have opened new horizons for the non-invasive diagnosis of NIH. Localization and size of periventricular-intraventricular haemorrhage (i.e. morphologic findings) are statistically related to mortality rate as well as to the later neurological outcome. In individual cases, however, additional biochemical and neurophysiological examinations (e.g. acid-base status, EEG, cortical and brain-stem evoked potentials) are necessary for the exact prognostic evaluation. The aim of our study was to examine whether cardiorespirography can help in defining the neurological status in very small newborns with and without clinical signs of CNS damage. Quantification of fetal heart rate variability during the ante-partum period is a useful complementary method for objective analysis of cardiotachograms [ 11.Pattern analysis and interval histograms of heart rate as well as respiration frequency are used as quantitative parameters, e.g., to assess the maturity of preterm born infants or to predict the probability of apneic attacks. V;ilim;iki et al., calculating an auto-correlation function, in this way could distinguish several particular reaction
Treatment and outcome of intracranial hemorrhage P.M. Fitzhardinge, Department of Pediatrics, Unioersity of Toronto, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario MSG 1X5, Canada Computed tomography (CT) and ultrasound (U/S) surveys of the brains of very low. birthweight infants have shown a remarkably consistent incidence of germinal layer (GLH) and intraventricular hemorrhage (IVH). Most studies report such
hemorrhages in approximately 45% of infants with birthweights less than 1500 g with the majority of bleeds occurring in those under 1000 g. Therapy in the neonatal period has concentrated on the prevention of extensive degrees of hemorrhage and the complication of hydrocephalus. Other papers at this Congress have dealt with the pathogenesis of GLH and the obstetrical and neonatal measures used to reduce the incidence of bleeding. These measures are directed towards avoidance of situations likely to produce trauma and/or hypoxic-ischemic insults to the brain both during the intrapartum and neonatal period, as well as avoidance of wide swings of cerebral blood flow and blood osmolarity during the first few days after birth. Specific treatment for the prevention of IVH has been generally disappointing. A preliminary study by Donn et al. suggested that phenobarbitone, when given prophylactically to at-risk infants, may reduce the incidence of GLH/IVH [ 11.These workers reported a 71% reduction in hemorrhage in 30 very low birthweight infants when compared with 30 matched controls. No specific mechanism of action was suggested for the phenobarbitone effect. This study has since been repeated by other investigators who have failed to confirm the prophylactic effect [2,3]. Another approach to therapy has involved a drug known to have a stabilizing action on capillary wall integrity. Morgan, in a randomized controlled study of 70 low birthweight neonates, has reported a significant reduction in the incidence of GLH in those infants treated at 2 h of age with ethamsylate [4]. However, there was no difference in incidence of major bleeds or of neonatal death between the treated and control groups. Ventricular dilatation is an accompaniment of most major IVH and is persistent in approximately 25%. A varying number of cases with persistent dilatation show a progressive increase in intracranial pressure requiring a shunt procedure for hydrocephalus. Investigators have attempted to reduce the incidence of hydrocephalus by repeated lumbar punctures commencing either at the first evidence of IVH [5] or after the onset of progressive ventricular dilatation has occurred [6]. The results of these intervention measures are difficult to interpret due to lack of controls and to the fact that, in the majority of cases, the increased intraventricular pressure is temporary and ventricular size becomes stabilized without any intervention [7]. Nevertheless, in cases of acutely raised intracranial pressure, repeated lumbar or ventricular taps or the oral administration of glycerol may be helpful as a temporary measure until a shunt procedure can be performed. The neonatal mortality associated with GLH/IVH varies directly with the extent of the hemorrhage and the degree of prematurity of the baby. During 1977-78 there was a tendency in some centers to withdraw life supports for babies with extensive hemorrhage. During those years we had only one survivor in 13 infants under 1500 g with grade IV IVH [8]. In 1979, preliminary results from follow-up encouraged us to maintain aggressive support of all babies unless persistent seizures or abnormal posturing was present. A recent study from the same unit, of babies born in 1980 who weighed less than 1250 g and whose management followed the new policy, reported that 7 of 18 babies survived a grade IV IVH [9]. Prospective studies on the outcome of low birthweight infants with documented GLH/IVH suffer from small samples and short-term follow-up. Nevertheless, the results from different centers appear to be fairly consistent. The presence, per se, of
346
blood in the germinal layer or the ventricles does not increase the risk of subsequent cerebral palsy or mental retardation. Studies suggest that grade IV hemorrhage is associated with a greater risk for later handicap but the number of such survivors is still too small for statistical analysis. Schub et al. compared a’group of 33 babies of gestational age below 35 wk with GLH t IVH with a matched control group of 30 infants and showed no -difference in incidence of major or minor sequelae between the 2 groups [lo]. In a prospective, study of 62 surviving asphyxiated babies born during 1977-78 with birthweights less than 1500 g, we were unable to show any relationship between CT findings’ during the first 2 wk and neurodevelopmental status at 2 yr post-term except for the fact that hydrocephalus occurred only in infants with preceding IVH [8]. Seventeen of the 27 with grade II or III IVH were normal at 2 yr. In a similar study from the same unit using U/S to diagnose hemorrhage in a population of appropriate for gestational age babies with birthweights less than 125 1 g, Pape et al. reported 11 of 12 children to be normal at 9 mth post-term following grade I to III IVH compared with 16 of 23 without antecedent hemorrhage 191. However, only 2 of the 7 children with grade IV were normal: 4 developed major neurological sequelae, 1 had mild developmental delay. The incidence of intracranial hemorrhage in term neonates is unknown as no systematic population scanning has been reported but it appears to be much more common than suggested by autopsy studies. Flodmark et al. reported that intracranial hemorrhage was diagnosed by CT in 91 (61%) of 148 neonates weighing more than 2500 g who were scanned because of neurological symptoms [Ill. IVH was present in 8 (5%), subdural hemorrhage in 13 (9%), and hemorrhage into brain parenchyma in 17 (12%). Mortality was highest in those with IVH or parenchymal hemorrhage (25%). Therapy in the term infant has been directed towards alleviation of acutely raised intracranial pressure (a common early complication of parenchymal and IVH) either by surgical decompression, clot removal or shunt. Except for those with isolated subarachnoid hemorrhage, the outlook for term infants with intracranial bleeding appears to be considerably worse than for the premature counterpart. In a prospective 2 yr study of 62 term infants surviving postasphyxial encephalopathy, 15 presented with blood in the ventricles and/or brain tissue [ 121. Ten of the 15 developed handicapping sequelae. All 6 with IVH presented with severe hydrocephalus or quadriplegia. All 5 children with infratentorial parenchymal hemorrhage were severely handicapped. In contrast, 3 of the 5 with supratentorial parenchymal hemorrhage appeared normal at 2 yr. The remaining two developed severe cerebral palsy. In summary, the most effective treatment for intracranial hemorrhage seems to be a perinatal approach which minimizes hypoxic-ischemic insult to the brain. Both neonatal mortality and morbidity are dependent upon the gestation age. The incidence and attendant mortality of GLH/IVH is high in the very immature infant but hemorrhage per se does not appear to influence the risk for neurodevelopmental sequelae in the survivors unless there is an associated parenchymal hemorrhagic infarction. In the full term infant, on the other hand, while intracranial hemorrhage is much less common and less likely to be fatal than in the preterm infant, it is associated with a high incidence of neurodevelopmental sequelae of a very severe and handicapping nature.
347
References I. Donn SM, Roloff DW, Goldstein GW. Prevention of intraventricular haemorrhage in preterm infants by phenobarbitone: a controlled trial. Lancet 1981; ii: 215-217. 2. Morgan MEI. Massey RF, Cooke RWI. Does phenobarbitone prevent periventricular hemorrhage in very low-birth-weight babies?: A controlled trial. Pediatrics 1982; 70: 186- 189. 3. Hope PL, Stewart AL, Thorburn RJ, et al. Failure of phenobarbitone to prevent intraventricular haemorrhage in small preterm infants. Lancet 1982; i: 444-445. 4. Morgan MEI, Benson JWT, Cooke RWI. Ethamsylate reduces the incidence of periventricular haemorrhage in very low birthweight babies. Lancet 1981; ii: 830-831. 5. Mantovani JF, Pasternak JF, Mathew OP. et al. Failure of daily lumbar punctures to prevent the development of hydrocephalus following intraventricular hemorrhage. J Pediatr 1980; 97: 278-281. 6. Papile LA, Burstein J, Burstein R, et al. Posthemorrhagic hydrocephalus in low-birth-weight infants: treatment by serial lumbar punctures. J Pediatr 1980; 97: 273-277. 7. Levene MI, Starte DR. A longitudinal study of post-haemorrhagic ventricular dilatation in the newborn. Arch Dis Child 1981; 56: 905-910. 8. Fitzhardinge PM, Flodmark 0, Fitz CR, et al. The prognostic value of computed tomography of the brain in asphyxiated premature infants. J Pediatr 1982; 100: 476-481. 9. Pape. K, Bennett-Britton S, Szymonowicz W, et al. Relationship of neonatal brain hemorrhage to death and neurodevelopmental outcome. Pediatr Res 1982; 16: 338A. 10 Schub HS, Ahmann PA, Dykes FD, et al. Prospective long-term follow-up of prematures with subependymal/intraventricular hemorrhage. Pediatr Res 198 1; 15: 7 Il. 11 Flodmark 0, Fitz CR, Harwood-Nash DC. The CT diagnosis of intracranial hemorrhage and hypoxic/ischemic brain damage in neonates. J Comput Assist Tomogr 1980; 4: 775-787. 12 Fitzhardinge PM, Flodmark 0, Fitz CR, et al. The prognostic value of computed tomography as an adjunct to assessment of the term infant with postasphyxial encephalopathy. J Pediatr 1981; 99: 771-78 1.
Diagnostic value of cardiorespirography K. Jahrig, Universitiits-Kinderklinik,
in neonatal intracranial haemorrhage
Soldtmanstr.
1.5, DDR-2200
Greifswald,
(NIH) G.D.R.
Introduction
Computerized tomographic and real-time ultrasonic scanning have opened new horizons for the non-invasive diagnosis of NIH. Localization and size of periventricular-intraventricular haemorrhage (i.e. morphologic findings) are statistically related to mortality rate as well as to the later neurological outcome. In individual cases, however, additional biochemical and neurophysiological examinations (e.g. acid-base status, EEG, cortical and brain-stem evoked potentials) are necessary for the exact prognostic evaluation. The aim of our study was to examine whether cardiorespirography can help in defining the neurological status in very small newborns with and without clinical signs of CNS damage. Quantification of fetal heart rate variability during the ante-partum period is a useful complementary method for objective analysis of cardiotachograms [ 11.Pattern analysis and interval histograms of heart rate as well as respiration frequency are used as quantitative parameters, e.g., to assess the maturity of preterm born infants or to predict the probability of apneic attacks. V;ilim;iki et al., calculating an auto-correlation function, in this way could distinguish several particular reaction