Peri-intraventricular Hemorrhage Research Articles

Prognosis and evolution of bilateral grade III intraventricular - hemorhages (III-III-IVH)

OBJECTIVE: To describe the evolution of bilateral III IVH so as to define optimal dates for therapeutic moves.METHODS: Longitudinal study of brain ultrasound scans from day 1 over the first three months of life. Our team calls "massive III" a hemorrhage with an intraventricular clot diameter >8mm on the coronal view at the level of Monro's foramina of the day of maximal hemorrhage. The 90 neonates were divided into four groups. Group I included 29 premature neonates who died in the first seven days after birth (birthweight (BW), 1,114 -/+253 g, gestational age (GA), 28 weeks 3 days); with 21 massive uni/bilateral grade III PIVH, and early filling of the whole ventricular system and cisterna magna. Group II included seven premature neonates who died in the second week after birth (similar in BW and GA, but more heterogeneous group). Two groups of infants survived for more than 14 days. Group III included 30 premature neonates (BW, 1,299 -/+260 g, GA, 29 weeks 1 day), with 20 classical grade III PIVH, who had post-hemorrhagic dilatation regressed spontaneously in 13 cases and regressed after acetazolamide treatment in 17 cases (five deaths due to three bronchopulmonary dysplasias and two periventricular leucomalacias). Group IV included 24 premature neonates (BW, 1,344 -/+289 g, GA, 29 weeks 5 days) with 15 massive grade III PIVH, who suffered posthemorrhagic hydrocephalus through obstruction of the Sylvius aqueduct (15) and/or of the cisterna magna (21), 12 blocks affecting both levels. Blocks were observed from day 8, and 35 in the quasi totality of cases (17 deaths).CONCLUSIONS: From 1,183 consecutive peri-intraventricular hemorrhages (PIVH) diagnosed by brain ultrasound studies (01/01/81-12/31/94), 90 were grade (III-III) PIVH, with a 36% overall survival. The massive volume of grade III PIVG plays a heavy role in early deaths of extremely low birthweight neonates and it heralds a blocked hydrocephalus in more vigorous infants who survive PIVH.

Multivariate autoregressive modelling combined with transcephalic electrical impedance: method to relate neonatal systemic circulation and respiration to cerebral circulation.

We studied the pulsatile component of cerebral circulation with transcephalic electrical impedance (delta Z) in six preterm newborns, three of whom had severe cerebral bleeding, peri-intraventricular haemorrhage (PIVH). The transcephalic electrical impedance delta Z signal, ECG, arterial blood pressure, (aBP) and respirogram were recorded on analogue magnetic tape for 30 min. Artefact-free stationary segments (lasting for 2 min) of the four signals were digitised. A digital multivariate autoregressive (MAR) model was used to study frequency-specific variability in the signals and to quantify interrelations between the variabilities of delta Z, HR, aBP and respiratory signals. MAR modelling describes a system where all the signals simultaneously explain each other. The inherent variability of delta Z was lower and the influences of respiration and aBP on delta Z significantly greater in infants with severe PIVH than in controls. These changes were observed at high frequencies corresponding to respiration and heart rate. This may be interpreted as a marker of pressure passivism in the cerebral circulation following PIVH. We conclude that in preterm babies the application of MAR modelling, together with transcephalic impedance, may be a new, helpful and quantitative method for the study of simultaneous interrelations between variables of cerebral and systemic circulations and respiration.

Cerebral circulation assessed by transcephalic electrical impedance during the first day of life--a potential predictor of outcome?

Pulsatile changes in intracranial blood volume (transcephalic electrical impedance, delta Z), arterial blood pressure (aBP) and respiration were studied during the first day after birth in 42 neonates with a birth weight of 1040-3850 g and gestational age of 26-36 weeks. The neurological outcome was assessed at 1 year of age to study the predictive ability of delta Z. delta Z, ECG, respirogram and direct aBP were recorded at 8-h intervals. Outcome was adverse in seven infants of whom two died from severe peri-intraventricular haemorrhage. PCO2 was higher (6.2 kPa) in the infants with adverse outcome than in those infants with favourable outcome (5.0 kPa) (P = 0.004). Blood glucose (4.5 vs. 3.3 mmol/l, P = 0.030) and first day administration of fluid (80 vs. 63 ml/kg/day, P = 0.003) behaved, respectively. Of the infants receiving dopamine therapy, 60% had adverse outcome while only 11% of those not receiving dopamine had adverse outcome (P = 0.016). Of the infants with high diastolic blood pressure levels, 32% had adverse outcome, while none with low diastolic blood pressure levels had adverse outcome (P = 0.031). Spectral analysis was used to examine signal variabilities in the frequency domain. During the first 24 h of life, the variabilities of aBP and respiration were equal in all the infants. The high-frequency delta Z signal variability (1.50-4.00 Hz, heart rate level) was found to be lower in the infants with adverse outcome (330 units) than in the infants with favourable outcome (1280 units, P = 0.017). The low delta Z variability allowed us to assume that there is a decrease of pulsatile cerebral blood flow (CBF) in the infants with adverse outcome. We speculate that this may result from the 'no reflow phenomenon', increased tissue pressure due to ischaemia and/or PIVH, the 'brain sparing effect' or constriction of main cerebral arteries due to increased pressure support or metabolic factors (PCO2, glucose). We believe that transcephalic impedance provides a potential cot-side method for monitoring cerebral circulation in the neonatal period with an ability to predict outcome.

Elevated arterial blood pressure is associated with peri-intraventricular haemorrhage

In a prospective study, brain ultrasound scans were performed in 42 newborns (median birth weight 1700 g, range 1020-3720 g; gestational age 32 weeks, 26-36) to reveal peri-intraventricular haemorrhage (PIVH) (grades I-IV) as well as echodensities (ED) and/or periventricular leucomalacia (PVL). ECG and arterial blood pressure were recorded on magnetic tape at 8-h intervals during the first 24 h of life for further computer analysis. Heart rate (HR) and its variability (HRV) indices RMSM (long-term variability) and RMSSD (short-term variability), together with their coefficients of variation, were computed. Systolic (SBP), diastolic (DBP), and mean blood pressures (MBP) were detected as average values for 2-min stationary segments together with the respective minima and maxima. The indices of variability and their coefficients of variation were computed for the arterial pressure. PIVH was found in 12 newborns and ED in 8 (of whom two developed PVL). The remaining 22 served as controls. Neither HR, HRV nor BP variability differed between the groups. DBP was higher in the group with PIVH (39 mmHg) when compared to both the controls (33 mmHg, P < 0.05) and the ED group (32 mmHg, P < 0.01). MBP behaved respectively (45 mmHg, 38 mmHg, 37 mmHg, P < 0.01). SBP behaved also similarly when gestational age and birth weight were used as covariates (57 mmHg, 48 mmHg, 47 mmHg, P < 0.01). Our results suggest that elevated diastolic, mean and systolic blood pressure are significantly associated with peri-intraventricular haemorrhage in preterm newborn infants.

Elevated arterial blood pressure is associated with peri-intraventricular haemorrhage

Elevated arterial blood pressure is associated with peri-intraventricular haemorrhage

CEREBRAL AUTOREGULATION IS A NONLINEAR TYPE CONTROL SYSTEM

Introduction. In neonates, low frequency (LF) cerebral blood flow velocity oscillations (CBFV-O) are commonly attributed to an underdampened immature cerebral autoregulation (AR). Peri-intraventricular hemorrhage (PIVH) is linked to this ‘instability’. In contrast to linear type control systems, nonlinear type systems express a regular periodicity as a fundamental part of their stable function. Aims. To classify the AR, and to identify factors possibly responsible for PIVF by investigating the relationship between CBFV-O, heart rate variability (HR-V), and intermittent positive pressure ventilation (IPPV). Methods. In 5 preterm neonates (GA 26 to 30 w) we serially Doppler-traced arterial CBFV continuously for 12 min every 3 to 7 days between days 1 and 49 of life. Another 5 preterms (GA 26 to 35 w) were traced sporadically. The time series of both CBFV and HR were subjected to spectral analysis. Results. 46/47 tracings showed LF CBFV-0 (p<0.0001, one sample z-test). For HR, cycling was observed in only 15/47 tracings. LF cycling in HR was not a prerequisite for LF CBFV-O. All patients with < 30 % of total power in the LF band of CBFV-O were on the ventilator. Three of these patients demonstrated a shift of spectral power from LF to a frequency equal or harmonic to the ventilator rate in the sense of entrainment. The range of entrainment encompassed 12 to 25/min stimuli. Conclusion. In analogy to thermo- and blood pressure regulation, CBFVO and entrainment classify the AR as a nonlinear system. HR-V has no direct impact on CBFV-O, whereas respiration acts on both HR-V and CBFV-O. We discuss that periodic high-amplitude stimuli (i.e. IPPV in RDS) may challenge the regulatory capacity of the CBF control system as reflected by entrainment. While fragile vascular matrix elements, severe central blood pressure changes, and high pCO2 are prerequisites, entrainment of CBFV-O might be one key event for cerebral damage.

Intracranial dynamics in pre-term infants and neonates: implications for physiotherapists

The control of cerebral circulation and intracranial dynamics differs markedly in the pre-term and full term neonate from that in the adult. Immaturity can combine with several clinical conditions and iatrogenic factors to predispose the neonate to cerebral lesions, which may subsequently increase morbidity. As physiotherapists play an increasingly important role in neonatology, it is important to appreciate the immaturity of the nervous system and to recognise the risk factors for such conditions as peri-intraventricular haemorrhage and periventricular leucomalacia. This paper describes intracranial dynamics in the pre-term and full term infant and illustrates how these factors may interact with clinical conditions to cause cerebral lesions. Studies which examine the effect of respiratory physiotherapy on intracranial dynamics are reviewed and suggestions made for further research.

Impact of Prematurity and Intrauterine Growth Retardation on Neonatal Hemorrhagic and Ischemic Brain Damage

Low birth weight and intrauterine growth retardation are well-recognized risk factors for increased mortality, morbidity and poor neurologic outcome. Risk assessment is different considering true preterm (appropriate-for-gestational-age, AGA) or growth-retarded (small-for-gestational-age, SGA) infants. Therefore, we carried out a study on the incidence of hemorrhagic (peri-intraventricular hemorrhage, PIVH) and ischemic (periventricular leukomalacia) brain lesions in two groups of AGA and SGA very-low-birth-weight (VLBW) infants. In the study period (1987-1990), 111 VLBW babies (< 1,500 g body weight) were serially studied at days 1, 3 and 7 and weekly until discharge by cerebral ultrasonography (ATL, MK 4, 7.5 MHz). 57 were VLBW-AGA babies (mean gestational age 28 weeks, mean body weight 1,106 g). 54 were VLBW-SGA babies (mean gestational age 31 weeks, mean body weight 990 g). PIVH was graded according to the system of Papile et al. Periventricular leukomalacia was defined as an echodensity (> 3 mm) adjacent to the lateral border of the ventricular body. We noted a higher incidence of PIVH in the AGA group (36.8%) than in SGA babies (18.5%; p < 0.01, Fisher test). The AGA subgroup < 1,000 g body weight had 72.2% PIVH compared to AGA babies > 1,000 g (20.5%; p < 0.01). The same relationship was observed in SGA babies (34.8% in < 1,000 g and 6.4% in > 1,000 g babies). Ischemic brain lesions (periventricular leukomalacia) were equally distributed between AGA and SGA babies (10.5 vs. 3.7%, p > 0.5) independently of body weight category.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurosonographic findings in premature infants and infants with intrauterine growth retardation with a birth weight below 1,500 grams

The cranial ultrasound of 111 preterm infants were reviewed. 57 patients were appropriate for gestational age (AGA) and 54 small for gestational age (SGA). In the two groups, the incidence of peri-intraventricular hemorrhage (PIVH), posthemorrhagic ventricular dilation (VM) and peri-ventricular leucomalacia (PVL) was compared. PIVH was more common in AGA than in SGA babies (36.8% vs 18.5%). In both groups (AGA and SGA), birth weight less than 1000 g should be considered a further risk factor for hemorrhagic brain lesion (72.2% in AGA babies less than 1000 g and 20.5% ind AGA babies greater than 1000 g birth weight, p less than 0.01) (34.8% in SGA babies less than 1000 g and 6.4% in SGA babies greater than 1000 g birth weight, p less than 0.05). However, ischemic brain lesions (PVL) were not dependent from birth weight (p greater than 0.5). This study shows that low birth weight infants are an eterogeneous group of babies with different risk of hemorrhagic or ischemic cerebral lesion depending on gestational age and birth weight.

Serum creatine-kinase-BB concentration in very low birth weight babies with posthemorrhagic ventricular dilatation

The association between measurements of lateral ventricle dilatation determined by serial ultrasound and brain specific creatine-kinase isoenzyme patterns (CK-BB) is studied in 60 very low birth weight preterm neonates of 1,500 g birth weight or 32 weeks gestation or less. The patients were divided into three groups according to cranial ultrasonographic findings: Group A (n = 20) had isolated peri-intraventricular hemorrhage (PIVH); group B (n = 20) had PIVH and dilated ventricles (VM); group C (n = 20) were normal matched preterms and formed the control group. Compared to control babies or those with isolated PIVH, high serum concentrations of CK-BB were observed after birth in babies with persistent dilated ventricles at two weeks postnatal age (p less than 0.01). No difference was found between CK-BB levels of babies with isolated PIVH and control group (p greater than 0.05). We suggest that an elevated CK-BB value is found in babies with persistent ventricular dilatation suggesting severe and diffuse brain damage after post-hemorrhagic ventriculomegaly (VM).

Intraoperative measurements of cerebral haemodynamics during ductus arteriosus ligation in preterm infants

Intraoperative Doppler sonographic examinations were carried out on seven preterm neonates to measure cerebral blood flow velocity changes in the anterior cerebral arteries during ductus arteriosus ligation. Age at surgery was 12 +/- 6 days. Continuous recordings during the operative procedure showed a rapid increase in diastolic blood pressure (P less than 0.01), whereas systolic blood pressure was not significantly higher compared with pre-occlusion values. In the anterior cerebral arteries, ductal closure led to a decrease in resistance index of Pourcelot (mean = 1.02 +/- 0.08 vs 0.65 +/- 0.07 (P less than 0.001)) and to an increase in area under the velocity curve (mean = 3.64 +/- 0.38 vs 8.16 +/- 1.07 (P less than 0.001)). These changes were associated with a corresponding increase of the end diastolic flow velocity (P less than 0.001) but no change in the peak systolic velocity. The heart rate did not change significantly during ductal closure. TcPO2, TcPCO2 remained normal during the study period. These data indicate that changes in cerebral blood flow velocity during surgical ligation are principally determined by changes in systemic diastolic pressure. Systolic blood pressure and peak systolic flow velocity remain unchanged or slightly higher than preligation values, thereby restoring normal cerebral blood flow velocity pattern without increasing the stress on the wall of cerebral vessels and thus the risk of peri-intraventricular haemorrhage.

Neurosonographic Assessment of Twin Pairs in the Perinatal Period

Twins have higher rates of perinatal mortality, prematurity and its complications, low birth weight, intrauterine growth retardation, congenital anomalies and long-term developmental morbidity. In 31 twin pairs we evaluated the incidence and severity of peri-intraventricular hemorrhage (PIVH) and post-hemorrhagic ventricular dilatation. On ultrasonography minor PIVH (grades I and II) was observed in 26% of A twins and 25% of B twins (p less than 0.5). Major PIVH (grades III and IV) was less common, occurring in 3% of A twins and 6% of B twins (p less than 0.5). Ventriculomegaly, mostly regressive was equally distributed between the two groups of babies. From these results it can be concluded that with efficient antenatal care and skillful perinatal management of twin pregnancy, the incidence of major perinatal neurological complications such as PIVH and ventriculomegaly are not higher in the second-born twin.

Determinants of visual evoked potentials in preterm infants

The latency and amplitude of NI, the first negative peak of single flash visual evoked cortical potentials (VEP) were evaluated in 86 preterm infants (25–34 weeks of gestation), investigated during the first day of life. All infants were regarded stable at the time of investigation and none had experienced severe asphyxia. Both the VEP latency and amplitude were inversely related to gestational age. When latency was corrected for age it was longer in boys than in girls. Age corrected VEP amplitude was inversely related to head circumference, umbilical cord pH and EEG activity. There was no difference between VEP parameters in asymmetrically growth retardated infants compared to those with normal growth. Administration of dexamethasone to the mother before delivery, mode of delivery, presence of hyaline membrane disease, mode of assisted ventilation or imminent development of peri-intraventricular haemorrhage did not affect the VEP.

Biochemical timing of peri-intraventricular hemorrhage assessed by perinatal CPK-BB isoenzyme measurements.

Precise diagnosis of peri-intraventricular hemorrhage (PIVH) requires brain real-time ultrasound imaging procedure (US). However, maximal diagnostic efficiency of US lies between day 4 and 14 since fresh blood may initially appear sonolucent. Because of this supposed interval required for clot formation to become visible on US, serum CPK-BB estimations were performed in the first 60 hours of life to determine precise biochemical timing of PIVH. A group of 50 preterm infants less than 1500 g birth weight (1120 +/- 320 g) and 34 weeks gestation (30 +/- 3.7 weeks) was studied. Serial CPK-BB measurements were performed in serum immediately after birth (T0), then serially at time T1 (6-10 h), T2 (20-30 h), T3 (40-60 h). The incidence of PIVH diagnosed on the third day of life was 30%. Total CPK-BB values at T0 in infants who developed PIVH were significantly higher than those of patients without cerebral bleeding (70.8 +/- 30.5 vs 20.9 +/- 10.7 U/l) (p less than 0.05). The same statistically significant results were not observed analysing the CPK-BB values at T1, T2 and T3. These results suggest that most pathological conditions responsible for enzyme release occur in the pre- or perinatal period.

Coagulation abnormalities in low birth weight infants with peri-intraventricular hemorrhage.

Fifty-four appropriate for gestational age preterm infants (less than 35 weeks gestation) were followed prospectively from birth with coagulation and real-time ultrasound studies. Coagulation analyses included fibrinogen, prothrombin time, thrombin time and platelet count. The occurrence of peri-intraventricular hemorrhage (PIVH) was documented by portable 5 MHz Echo Scanner. Definite PIVH was present in 21 babies (38%). Coagulation studies showed especially lower values of fibrinogen levels in babies of less than 30 weeks gestation compared to a control group without PIVH (p less than 0.03). Furthermore, significant correlation was observed in these patients between platelet count and degree of PIVH. Infants with Grade 3 and 4 PIVH had lower platelet count than infants with less severe bleeding (Grade 1 and 2) (p less than 0.02). These data suggest that hemostatic abnormalities play a major role as co-factor in the incidence and severity of neonatal PIVH in very low birth weight infants of less than 30 weeks gestation.

Neurodevelopmental outcome in cystic periventricular leukomalacia (CPVL) (30 cases).

Thirty infant survivors had a wide spectrum of neonatal cystic periventricular leukomalacia (CPVL) diagnosed by ultrasound scans: 11 minor forms, 12 moderate forms, 7 major forms (categorized by both sagittal extent and coronal thickness). Eight cases were pure CPVL and 22 were associated with minor to moderate peri-intraventricular haemorrhage (PIVH), i.e. from (0-I) to (II-II). Mean gestational age: 31 +/- 2 weeks; mean birthweight: 1,532 +/- 356 g. The length of neurodevelopmental (ND) follow-up ranged from 13 months to 3 years and eight months. Of 11 children with minor CPVL, 9 were normal and two had moderate sequelae. Of 12 moderate CPVL, one was lost to follow-up, one had no motor disturbance but did have severe mental retardation (partial 7 p-), two were normal, one had a minor sequela, three had moderate and four had severe sequelae. Of the 7 major CPVL, one had moderate and 6 had severe sequelae. Cases including posterior lesions or presenting solely with such lesions had a worse outcome. In that range of PIVH, the outcome was related to the severity of CPVL and not to PIVH grade. All major late dilatations were associated with severe ND sequelae. Of 29 infants with early EEG tracings, the 7 children with early severe EEG abnormalities all had severe ND sequelae; 17 persistent EEG abnormalities, even mild, were associated with 9 severe and five moderate ND sequelae, and three normal outcomes. Combining US scans and EEG gives valuable prognostic information in minor and major CPVL, but less in the moderate forms.

Relationship between peri-intraventricular hemorrhage and neonatal hyperbilirubinemia in very low-birthweight infants.

The incidence of hyperbilirubinemia (serum bilirubin values greater than 205 mumol/l) in two groups of preterm infants (birthweight less than 1500 gm) with and without peri-intraventricular hemorrhage (PIVH) was studied. In the first 10 days of life, 16 (39%) of the 41 infants with PIVH vs. 22 (46.8%) of those without PIVH (n = 47) had high bilirubin levels. No difference in peak serum bilirubin concentrations nor a need for phototherapy was noted between the two groups (P greater than 0.07). Forty-one infants had PIVH: 30 had PIVH grade I or II and 11 had grade III or IV. No statistically significant correlation was found between degree of PIVH and hyperbilirubinemia. Moreover, at 12 months corrected age, major and minor handicaps were equally distributed between the two groups. The neurologic outcome appeared to relate, in largest part, to the severity of the PIVH, and to not be influenced by the hyperbilirubinemia. We conclude that there is no positive relationship between incidence and extension of PIVH, plasma bilirubin levels, and outcome in very low-birth weight infants.

Aetiological rôle of cerebral blood-flow alterations in development and extension of peri-intraventricular haemorrhage.

The aetiology and extension of peri-intraventricular haemorrhage (PIVH) are thought to be related to cerebral blood-flow alterations, and especially to increased cerebral blood-flow and fluctuating velocity of blood-flow. Using transcutaneous Doppler technique, the authors investigated cerebral blood-flow in 60 infants with gestations of less than 34 weeks. Pulsatility index (PI) and area under the velocity curve (AUVC) of the anterior cerebral arteries (ACA) were used as qualitative measures of cerebral blood-flow, and the coefficient of variation of PI and AUVC as indicators of fluctuations in blood-flow velocity. A reasonable correlation was found between PI and AUVC and their coefficients of variation in the ACA. First onset of PIVH was related to fluctuating blood-flow velocity, and extension of PIVH with both increased velocity (indicating increased blood-flow) and fluctuating velocity. Increased cerebral blood-flow and its fluctuating pattern were positively correlated with arterial carbon dioxide tension.

Fetal sex and distribution of peri-intraventricular hemorrhage in preterm infants.

Peri-intraventricular hemorrhage (PIVH) is an important complication of the brain in immature newborn infants. In a real-time ultrasound study with frequent scanning of 78 preterm infants (50 with birth-weight less than 1,500 g and 28 weighing more than 1,500 g), we examined the influence of sex on the occurrence of PIVH. A significant difference between sexes was only found in the group with birth-weight below 1,500 g. PIVH occurred in 72% of male infants and in 28% of females (p less than 0.001). This effect is probably due to a difference in the timing of cerebral vascular maturation in males leading to a difference in the risk of developing PIVH between the sexes before 34 weeks of gestation.

Incidence of peri-intraventricular hemorrhage in premature neonates weighing more than 1500 g.

With the advent of modern methods of neonatal care, intracranial hemorrhage probably has become the most common neurological complication in premature infants weighing less than 1500 g at birth. This paper is a prospective study of 75 preterm infants of 34 weeks gestation or more and birth weight above 1500 g (range 1500 g to 2500 g). All neonates were screened by cranial ultra-sonography for evidence of peri-intraventricular hemorrhage (PIVH). Perinatal risk factors, incidence of PIVH and neurological outcome were studied. Sonographic abnormalities were detected in 16 (21.3%) of our patients. Intracranial hemorrhage was frequently associated with a low Apgar score, need of resuscitation and/or assisted ventilation immediately after birth (P less than 0.005). This study suggests, that ultrasound screening should be reserved to those large premature infants (greater than 1500 g) with high risk of hypoxic-ischemic injury.