Head size,brain growth,and lateral ventricles in very low birthweight infants.

Ninety eight newborn infants weighing less than 1500 g at birth and with gestational ages from 26 to 32 weeks were followed prospectively. They were grouped according to real time ultrasound scans in the neonatal period: infants in group A (n = 20) had periventricular haemorrhage (PVH) and normal ventricles; infants in group B (n = 26) had PVH and dilated ventricles (none with clinical hydrocephalus); and infants in group C, who formed the control group (n = 52), had no PVH and normal ventricles. At outpatient follow up a static image ultrasound scanner was used to measure the width of the lateral ventricles and brain hemispheres. The three groups of infants showed similar growth in occipitofrontal circumference, biparietal diameter, and brain hemispheres irrespective of a history of PVH or ventricular dilatation. The relation of ventricle size to biparietal diameter was similar in those infants in groups A (PVH alone) and C (controls) who had a good outcome. About a third (n = 8) of the infants in group B had persistent ventricular dilatation in relation to biparietal diameter and a poor outcome associated with developmental delay and cerebral palsy. By contrast, the remaining two thirds (n = 18) of the infants in group B who later had smaller ventricles in relation to biparietal diameter showed fewer neurodevelopmental sequelae. It is suggested that persistent ventricular dilatation in relation to biparietal diameter at follow up carries a bad prognosis, which might be due to brain atrophy.     

Neurodevelopmental outcome of periventricular haemorrhage and leukomalacia in infants 1250 g or less at birth

The brains of 50 consecutively admitted infants weighing 1250 g or less at birth were serially examined beyond the neonatal period for periventricular haemorrhage and for periventricular leukomalacia with real-time ultrasound. There was significant correlation between the presence or absence and the severity of haemorrhage with survival. A prospective neurodevelopmental assessment was completed at 2 years of age, corrected for prematurity, on all survivors. None of the 20 survivors with normal scans or germinal layer haemorrhages had evidence of major disability and all four survivors with intracerebral haemorrhage or periventricular leukomalacia had major disability. The mental performance on the Bayley scales of infant development was also significantly worse in the latter group. Six of the eight survivors with intraventricular haemorrhage had no major disability, including three who had post-haemorrhagic hydrocephalus. Our results showed that cerebral ultrasound detection of brain pathology is a good predictor of neurodevelopmental outcome in such extremely low birthweight infants. However, as the maximum extent of periventricular haemorrhage may develop beyond one week of age and cystic periventricular leukomalacia commonly develops after the neonatal period, serial scanning is mandatory to ensure diagnostic accuracy for both periventricular haemorrhage and leukomalacia.     

Periventricular leucomalacia and neurodevelopmental outcome in preterm infants.

During an 18 month period, 120 preterm infants of 34 weeks'' gestation or less were prospectively examined for periventricular leucomalacia (PVL) by cerebral ultrasound. Neurological and developmental assessment was carried out at 18 months of age corrected for prematurity in 82 surviving neonates. The developmental outcome (Griffiths development quotient) was above 80 and similar in infants with normal scans (n = 41), isolated periventricular-intraventricular haemorrhage (n = 13), and post-haemorrhagic hydrocephalus (n = 4), and no major handicap was diagnosed in these groups. By contrast, the prognosis was variable and poorer in infants with PVL (n = 24) and depended on the extent and site of the lesion. Infants with frontal PVL (n = 13) developed normally. Major sequelae (n = 8) were closely related to frontal-parietal PVL and frontal-parietal-occipital PVL and could be ascribed to the presence of cysts as well as to a persistent hyperechogenic ultrasonographic PVL appearance. A relation between size and site of the lesion and type and severity of the handicap was established.     

Ultrasound and necropsy study of periventricular haemorrhage in preterm infants.

The diagnostic accuracy of cerebral ultrasound for periventricular haemorrhage was determined by comparing this with necropsy findings in 30 preterm neonates of 30 weeks'' gestation or less and birthweight under 1500 g. Ultrasound gave an accurate diagnosis of 85% in infants with germinal layer haemorrhage, 92% in intraventricular haemorrhage, and 97% in intracerebral haemorrhage. False positive errors were caused by vascular congestion; false negative errors occurred when the maximum dimension of haemorrhage was less than 3 mm. Cerebral ultrasound gave a diagnostic accuracy of 63% for periventricular leucomalacia. False negative errors occurred when periventricular leucomalacia was microscopic or when it was out of range of the scanner. The maximum width of the germinal layer was measured in 77 neonates of gestational age 23 to 36 weeks who died and had no periventricular haemorrhage at necropsy. The progressive involution of the germinal layer with increasing gestational age paralleled the steady decrease in incidence of periventricular haemorrhage diagnosed over the same gestational age range. Neonates of the youngest gestational age who had the most extensive germinal layers also had the highest risk for periventricular haemorrhage.     

Etiological Factors Associated with the Development of Periventricular Leukomalacia

ABSTRACT. Prenatal, intrapartum and postnatal factors are compared between 15 preterm infants, known to have periventricular leukomalacia (PVL) on ultrasound and 15 infants of similar birthweight and gestation who ultrasonographically showed no evidence of cystic lesions, and who are known to be neurologically normal at follow up. Prenatally, the incidence of antepartum haemorrhage was significantly higher in the PVL group. Intrapartum factors were similar between the two groups but postnatally, the PVL group had significantly lower PaCO₂ readings during the first 72 h of life. It is postulated that a severe maternal bleed in late pregnancy and neonatal hypocarbia could significantly decrease cerebral perfusion and cause areas of ischaemia and infarction resulting in periventricular leukomalacia.     

Etiological factors associated with the development of periventricular leukomalacia

Prenatal, intrapartum and postnatal factors are compared between 15 preterm infants, known to have periventricular leukomalacia (PVL) on ultrasound and 15 infants of similar birthweight and gestation who ultrasonographically showed no evidence of cystic lesions, and who are known to be neurologically normal at follow up. Prenatally, the incidence of antepartum haemorrhage was significantly higher in the PVL group. Intrapartum factors were similar between the two groups but postnatally, the PVL group had significantly lower PaCO2 readings during the first 72 h of life. It is postulated that a severe maternal bleed in late pregnancy and neonatal hypocarbia could significantly decrease cerebral perfusion and cause areas of ischaemia and infarction resulting in periventricular leukomalacia.     

A longitudinal study of post-haemorrhagic ventricular dilatation in the newborn.

Two hundred and two consecutive admissions to a regional neonatal unit were scanned by real-time ultrasound. Sixty-eight (34%) infants had intracranial haemorrhage, 39 (57%) of whom were scanned repeatedly until they were at least 30 days old. Fifteen infants showed some degree of ventricular dilatation. Four had transient dilatation with complete recovery without any form of treatment (group 1), 7 showed persistent but non-progressive dilatation with no treatment (group 2), 3 had rapidly progressive hydrocephalus (group 3), and 1 had cerebral atrophy (group 4). Occipitofrontal head circumference was also followed sequentially from birth and was not abnormal in groups 1 and 2, but abnormal rates of head growth were seen in groups 3 and 4. It is concluded that after intracranial haemorrhage only a small proportion of infants develop frank hydrocephalus, but ventricular dilatation of some degree is common and may require no treatment.     

Neonatal intracranial lesions following placenta abruption

A case-controlled study of the cerebral ultrasound appearances of neonates following placental abruption was undertaken. Twenty-nine index subjects (median gestation 29 weeks) were identified over a 2-year period with gestation-and sex-matched controls. Placental abruption was associated with a fourfold increased incidence of periventricular leukomalacia and extensive periventricular haemorrhage, without increased mortality. Ten infants (34%) developed cystic periventricular leukomalacia following placental abruption, compared with three (10%) in the control group. Intraventricular haemorrhage (excluding subependymal haemorrhage) and haemorrhage into the brain parenchyma occurred in 21 (72%) infants in the abruption group, compared with 14 (48%) in the control group (P<0.05).     

Timing and antecedents of periventricular haemorrhage and of cerebral atrophy in very preterm infants

The brains of 95 consecutively admitted infants born at less than 33 weeks gestation were scanned with ultrasound. Thirty-six (38%) had periventricular haemorrhage (PVH). Eight (8%) had cerebral atrophy (together with PVH in 5).Twelve (40%) of the 30 infants in whom satisfactory timing of PVH was possible bled on the first day of life, but the median age when PVH was first detected was during the second day. The median age when PVH reached its maximum extent was the fourth day. The most significant antecedents of PVH were very short gestation and the presence of severe respiratory illness, particularly hyaline membrane disease, necessitating mechanical ventilation. Analysis of variance showed that pneumothorax arising during ventilation was the single most significant antecedent of PVH. Other significant antecedents, notably prolonged coagulation times, were found almost exclusively in infants with severe respiratory illness.Cerebral atrophy appeared usually to be attributable either to severe asphyxia during delivery or later, or to the formation of cysts at the site of previous haemorrhage into brain tissue.     

Periventricular leucomalacia and intraventricular haemorrhage in the preterm neonate.

Two hundred very low birthweight infants were prospectively scanned to ascertain the incidence of periventricular leucomalacia (PVL) and haemorrhage. Before collection of data, clear definitions of ultrasound abnormalities believed to represent PVL and intraventricular haemorrhage were described. These referred to small and moderate intraventricular haemorrhage, paenchymal haemorrhage, and PVL, including prolonged flare (echoes in the periventricular region lasting for two weeks or more and not becoming cystic). Sixty nine infants (34%) had no abnormality on ultrasound scans. Intraventricular haemorrhage occurred in 107 babies (37 grade I and 62 grade II), and only eight infants were thought to have true parenchymal haemorrhage. Ultrasound appearances of PVL were seen in 27 infants, 19 of whom developed cysts and eight died in the precystic stage. Prolonged flare occurred in another 25 babies. Unilateral parenchymal haemorrhage occurred in four infants who subsequently developed cystic PVL in the contralateral hemisphere. Twenty one infants developed ventricular dilatation, 12 of whom had associated parenchymal lesions. Haemorrhage, PVL, and flare occurred commonly in infants of 30 weeks'' gestation and below and became markedly less common in more mature infants. We believe prolonged flare represents a form of PVL, and in this study a total of 52 (26%) infants had an ultrasound appearance of periventricular leucomalacia, an incidence considerably higher than previously reported.     

Effect of neonatal periventricular haemorrhage on neurodevelopmental outcome.

All 56 infants born between 23 and 28 weeks'' gestation admitted to this hospital in 1981 were examined for periventricular haemorrhage with cerebral ultrasonography. Haemorrhage was diagnosed in 34 (61%)-12 (22%) had germinal layer haemorrhage, 18 (32%) had intraventricular haemorrhage, and four (7%) had intracerebral haemorrhage. The two year outcome of survivors with and without periventricular haemorrhage was compared to determine the effect on neurodevelopment. Only three (16%) of 19 infants with normal scans or germinal layer haemorrhages had evidence of major disability but nine (75%) of 12 infants with intraventricular or intracerebral haemorrhage had major disability. The mental and psychomotor performance on the Bayley scales of infant development was also significantly worse in the latter group. All three survivors with intracerebral haemorrhage had major disability. The continuation of life support treatment for extremely preterm infants who are at very high risk of severe handicap is a matter of increasing concern in neonatal intensive care. Our results show that if extensive periventricular haemorrhage, in particular intracerebral haemorrhage, occurs in this gestational group, extreme pessimism is warranted.     

Structure and evolution of echo dense lesions in the neonatal brain. A combined ultrasound and necropsy study.

Sixty seven of 216 infants weighing less than 2 kg at birth had cerebral lesions on ultrasonic scanning. Eight of 17 who had periventricular leukomalacia, with or without subependymal or intraventricular haemorrhage, or both, died. These and one larger baby were the subject of a combined ultrasound, and where appropriate, necropsy study. There was excellent correlation between the ultrasound and necropsy findings, only some of the earlier lesions of periventricular leukomalacia being missed by ultrasound. The data suggest it is now possible to distinguish periventricular leukomalacia and subependymal/intraventricular haemorrhage by ultrasound, that both lesions may be present in the same brain, that apparent parenchymal extension of an intraventricular haemorrhage is more probably the result of haemorrhage into ischaemic periventricular tissue, and that the term ''periventricular haemorrhage'' should be abandoned since it confuses two lesions of differing aetiology and differing clinical importance. Future advances in neonatal brain ultrasound depend on accurate assessment of both the nature and site of lesions within the cerebral hemispheres and ventricular system since the interpretation of these parameters is of critical importance.     

Timing and evolution of periventricular haemorrhage in infants weighing 1250 g or less at birth.

The brains of 50 consecutively admitted infants who weighed 1250 g or less at birth were examined with real time ultrasound. Of 30 (60%) who had periventricular haemorrhage (PVH), 19 (63%) bled on the first day and 17 (57%) showed extension of the initial haemorrhage on serial scans. The median age was 16 hours when PVH was first detected and 48 hours when PVH reached its maximum extent. Ventricular size at birth correlated with gestation. Progressive ventricular growth was seen after birth in infants both with and without PVH. Charts of normal ranges of ventricular size and head circumference were drawn up from birth to 10 weeks of age. All infants with PVH showed a transient increase in ventricular size at 2 weeks of age but most returned to normal by 6 weeks of age. Ventricular dilatation after PVH that was greater than the 95th centile for this population developed in 5 (31%) of 16 survivors, four of whom subsequently developed hydrocephalus, although none required ventriculo peritoneal shunting. The optimal timing for diagnosis with ultrasound is at the end of the first week for PVH and the second to third week for ventricular dilatation.     

Cranial ultrasound abnormalities in full term infants in a postnatal ward: outcome at 12 and 18 months

OBJECTIVE: To investigate whether cranial ultrasound abnormalities found in low risk full term infants had any influence on neurodevelopmental outcome. METHODS: For 103 infants who had a neurological assessment, a cranial ultrasound examination, and for whom antenatal and perinatal data were collected within 48 hours of delivery, neurodevelopmental status was evaluated at 12 and 18 months. The results of a scored neurological examination and the Griffiths mental developmental scale were correlated with the presence and type of ultrasound abnormality found in the neonatal period. RESULTS: None of the infants with ultrasound abnormalities showed any signs of cerebral palsy or severe developmental delay. There was also no significant difference between the overall neurological and neurodevelopmental scores of the infants with normal and abnormal ultrasound findings. However, when the individual subscales of the Griffiths test were analysed, all infants with bulky choroid or intraventricular haemorrhage had normal scores in all subscales, four of eight with periventricular white matter lesions had low scores on the locomotor subscale, and three of five with asymmetrical ventricles had low scores on the performance subscale. The presence of adverse antenatal and perinatal factors did not affect the outcome in this group. CONCLUSION: Incidental ultrasound abnormality in full term neonates, in particular intraventricular haemorrhage, although common, appear to have a good prognosis. Longer follow up studies are needed to see whether some of these infants, in particular those with white matter lesions, develop dyspraxia or other minor neurological impairments at school age.     

Outcome of intrauterine periventricular haemorrhage and leukomalacia

This case study reports five very low birthweight infants with ultrasound evidence of intrauterine insult to the brain. Intrauterine periventricular haemorrhage (PVH) accompanied by ventricular dilation occurred in two preterm infants both of whom survived and were severely handicapped at follow-up. Three preterm infants had intrauterine periventricular leukomalacia (PVL); one survived and is severely handicapped at one year of age. Our experience and rare case reports in the literature indicate that intrauterine PVH and PVL carry a high risk of death in neonatal period and severe neurological sequelae in survivors.     

Outcome of intrauterine periventricular haemorrhage and leukomalacia

This case study reports five very low birthweight infants with ultrasound evidence of intrauterine insult to the brain. Intrauterine periventricular haemorrhage (PVH) accompanied by ventricular dilatation occurred in two preterm infants both of whom survived and were severely handicapped at follow-up. Three preterm infants had intrauterine periventricular leukomalacia (PVL); one survived and is severely handicapped at one year of age. Our experience and rare case reports in the literature indicate that intrauterine PVH and PVL carry a high risk of death in the neonatal period and severe neurological sequelae in survivors.     

Factors affecting survival and outcome at 3 years in extremely preterm infants.

A total of 823 infants born at 28 weeks' gestation or less were admitted to a regional referral unit between 1980 and 1989. Four hundred and sixty five (56.5%) survived to be discharged home. Twenty one subsequently died and two were lost to follow up. Four hundred and forty two (53.7%) were assessed for disabilities at the age of 3 years. Eighty four (19%) had major disabilities, of which 40 (9%) were severe. A further 39 (9%) had lesser disabilities. Three hundred and nineteen (63%) survivors appeared to be functioning normally. Logistic regression showed the likelihood of survival to be independently related to gestational age, birthweight ratio, and more recent year of birth, and inversely related to male sex and ultrasound evidence of cerebral haemorrhage or infarction. The likelihood of later disability in survivors was only independently related to cerebral ultrasound appearances.     

Salmonella meningitis and its complications in infants

OBJECTIVE: To review the presenting features, complications and outcome of infants with Salmonella meningitis. METHODOLOGY: Retrospective review of all cultures of cerebrospinal fluid positive for bacteria in children below 12 years of age, processed at the Department of Medical Microbiology, University of Malaya Medical Centre, Kuala Lumpur from 1973 to 1997. Records of all cases positive for Salmonella species were retrieved and studied. RESULTS: Thirteen infants aged 3 days to 9 months with Salmonella meningitis were included. The median age of onset of symptoms was 4 months. The clinical and laboratory features were similar to other causes of bacterial meningitis. Salmonella enteritidis was the commonest serotype isolated. Nine infants developed fits, six of which were difficult to control. Other complications noted were hydrocephalus (five), subdural effusions (four), empyema (three), ventriculitis (two), intracranial haemorrhage and cerebral abscess (one each). The use of ampicillin and/or chloramphenicol and inadequate duration of therapy resulted in recrudescence or relapse in five infants. The overall mortality was 18%. The presence of empyema, intracerebral abscess, ventriculitis, hydrocephalus, and intracranial haemorrhage were associated with adverse neurodevelopmental sequelae or death. More than half of those who survived had normal long-term outcome. CONCLUSION: Infants who developed neurological complications as a result of Salmonella meningitis had significant mortality and adverse long-term neurodevelopment outcome.     

A study of cerebral perfusion using single photon emission computed tomography in neonates with brain lesions

In this study we used a single photon emission computed tomography technique (SPECT) with radiolabelled ^99mTc HMPAO to assess cerebral perfusion in newborn infants with documented cerebral lesions and to determine to what extent brain SPECT might be useful in the neonatal period. A total of 15 newborn infants with the following cerebral pathologies were enrolled: severe parietal bilateral periventricular leucomalacia (PVL, n = 6); moderate parietal bilateral PVL ( n = 2); intraventricular haemorrhage grade II with unilateral parietal parenchymal extension (IHV + PE, n = 3); cerebral infarction (CI, n = 2) in the zone of middle cerebral artery; and post-haemorrhagic hydrocephalus ( n = 2). Follow-up was available in all infants. Alterations in cerebral perfusion were seen in only 12 of 15 infants and at the location of severe PVL, PE and CI. We have noted that the regions of diminished perfusion extended, beyond the apparent extent of cerebral pathology delineated by ultrasound or magnetic resonance imaging. Markedly diminished perfusion was seen in 1 infant with hydrocephalus, which recovered following placement of ventriculo-peritoneal shunt. Regarding outcome, SPECT data failed to provide additional information than that of neuroradiological investigations. We conclude that the use of SPECT, under these conditions, to assess alteration of cerebral perfusion in the neonatal period will not provide any additional information than that of neuroradiological investigations.     

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.