Neuroprotection of the developing brain by systemic administration of vasoactive intestinal peptide derivatives.
(1/192)
Periventricular leukomalacia (PVL), a necrotic and often cystic lesion of the cerebral white matter occurring in very premature babies, is the leading cause of cerebral palsy in this population. Increased glutamate release and the excitotoxic cascade thus triggered may be critical factors in the development of PVL. The glutamatergic analog ibotenate injected intracerebrally into newborn mice produces white matter cysts that mimic human PVL. Concomitant injection of vasoactive intestinal peptide (VIP), a trophic factor, protects the white matter against excitotoxic lesions. The goal of the present study was to assess the protective properties of systemically injected VIP analogs against ibotenate-induced excitotoxic white matter lesions in newborn mice. VIP analogs were selected on the basis of their low susceptibility to endopeptidases and their potential ability to cross biological membranes. RO-25-1553, a long-lasting cyclic VIP analog, and stearyl-norleucine-VIP, a fatty derivative of VIP, reduced ibotenate-induced white matter cysts by up to 87% and 84%, respectively, when injected i.p. immediately after ibotenate. By comparison, i.p. coadministration of VIP and ibotenate was not protective against the excitotoxic insult. Furthermore, RO-25-1553 and stearyl-norleucine-VIP still induced significant neuroprotection of the developing white matter when injected systemically 8 and 12 h, respectively, after ibotenate, establishing these peptides as therapeutic agents in this murine model. VIP analogs may have therapeutic potential in human premature babies at high risk for PVL. (+info)
Neurological morbidity after fetal supraventricular tachyarrhythmia.
(2/192)
BACKGROUND: Fetal tachyarrhythmia is a well-documented entity which, in the absence of pharmacological intervention, may lead to congestive heart failure, fetal hydrops and eventually fetal demise. The success rate of the implemented treatment is generally measured by survival and achievement of control of the arrhythmia. We report on the occurrence of associated cerebral damage in three patients with fetal tachycardia. METHODS: We describe three patients with a history of fetal supraventricular tachyarrhythmia who developed cerebral complications in utero. RESULTS: Two patients had cerebral hypoxic-ischemic lesions and one had hemorrhagic lesions present at birth. They had developed severe congestive heart failure and fetal hydrops secondary to fetal tachyarrhythmia, and there were no other obvious causes for the cerebral pathology. Two of these patients were referred to us antenatally. Therapy was instituted and resulted in control of the tachycardia and resolution of hydrops. The third patient was referred to our clinic shortly after birth because of severe circulatory problems secondary to fetal tachyarrhythmia. CONCLUSION: From these observations, we believe that a fetus with tachyarrhythmia and subsequent hydrops is at increased risk for the development of cerebral complications, due to the circulatory disturbances and sudden changes in heart rate which may lead to fluctuations in cerebral perfusion. This would imply that it is of the utmost importance to aim at immediate and complete control of the heart rate in the treatment of fetal tachyarrhythmia. (+info)
Periventricular leucomalacia and preterm birth have different detrimental effects on postural adjustments.
(3/192)
Postural adjustments during sitting on a moveable platform were assessed by means of multiple surface EMGs of neck, trunk and leg muscles and kinematics in three groups of children, aged 1 1/2-4 1/2 years. The first group consisted of 13 preterm children (born at a gestational age of 25-34 weeks), whose neonatal ultrasounds had shown distinct lesions of the periventicular white matter (PWM). The second group was the preterm control group, consisting of 13 preterm children with normal neonatal brain scans, matched to the PWM group with respect to gestational age at birth, birth weight, sex and age of postural assessment. The third group was formed by 13 healthy children born at term and matched to the PWM group with respect to sex and age at examination. In addition to the postural assessment an age-specific neurological examination was carried out. Three of the children of the PWM group developed a cerebral palsy syndrome, nine showed minor neurological dysfunction and one child was neurologically normal. In the preterm control group one child showed minor neurological dysfunction, while the remaining 12 children of this group and all children of the full-term group were neurologically normal. The postural assessment revealed that preterm birth was associated with two types of postural dysfunction. One dysfunction was related to the presence of a PWM lesion and consisted of a limited repertoire of response variation. The other dysfunction was not related to the presence of a PWM lesion, but to preterm birth itself. It consisted of a change in the ability to modulate the postural responses. Preterm children showed a higher sensitivity to platform velocity than full-term children, and they lacked the capacity to modulate EMG amplitude with respect to initial sitting position. (+info)
Trends in incidence of cranial ultrasound lesions and cerebral palsy in very low birthweight infants 1982-93.
(4/192)
AIM: To evaluate the effects of changing perinatal practice on outcome in terms of cranial ultrasound appearances and subsequent cerebral palsy rates in survivors. METHODS: A tertiary neonatal centre based prospective cohort study was undertaken of very low birthweight infants, in three 4 year periods: 1982-5, 1986-9, 1990-3. Rates of survival, parenchymal cerebral haemorrhage (PH), and leucomalacia on cerebral ultrasound scans, and cerebral palsy (CP) at the age of 3 years were compared. Antenatal steroid prophylaxis and postnatal surfactant use were also compared. RESULTS: VLBW infants (1722) were admitted over the 12 years, of whom 1268 (73.6%) were discharged home. Neonatal survival increased significantly over the three periods (69.2%, 72.9%, 79.7%; p < 0.0001). PH declined from 14.9% to 10.5% (p = 0.032) after 1990 as did CP rate (10.9% to 7.3%; p = 0.046). The use of antenatal steroids and postnatal surfactant greatly increased during this period. Steroid use was significantly associated with increased survival (OR 3.34, 2.31-4.79), decreased PH (OR 0.44, 0.28-0.71), and decreased risk of CP in survivors (OR 0.47, 0.27-0.81) after standardising for gestation, birthweight, sex, place and mode of delivery. Similar effects for surfactant did not remain significant after steroid use had been accounted for. CONCLUSION: Improved survival in VLBW infants since 1990 has been accompanied by a fall in PH and subsequent CP rates in survivors. This change is most likely to be due to the greater use of antenatal steroid prophylaxis. (+info)
Meta-analysis of elective high frequency ventilation in preterm infants with respiratory distress syndrome.
(5/192)
AIM: To summarise the evidence on the efficacy of elective high frequency ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome. METHODS: A search from 1987 onwards was made on Embase, Medline, and the Cochrane Library. A questionnaire was also circulated during an international meeting on high frequency ventilation. To be included in the data synthesis, studies had to be randomised controlled trials comparing elective high frequency ventilation with conventional ventilation in preterm infants with respiratory failure due to respiratory distress syndrome; indices of mortality, chronic pulmonary morbidity, and other clinically relevant outcomes were compared. Studies were assessed for methodological validity according to explicit criteria. RESULTS: Ten studies (a total number of 1345 preterm infants) were considered for data synthesis. No difference in mortality at 28 or 30 days, nor in oxygen dependency at 28 days was found between both types of ventilation. Reduced oxygen dependency at the postconceptional age of 36 weeks (RR 0.50, 95% CI 0.32-0.78) was found, but so was an increase in grades 3 and 4 intraventricular haemorrhage (IVH) (RR 1.31, 95% CI 1.04-1.66). Those studies using a high lung volume ventilatory strategy showed a significant decrease in oxygen dependency at the postconceptional age of 36 weeks (RR 0.44, 95% CI 0.27-0.73), but no increase in severe IVH (RR 0.78, 95% CI 0.45-1.37). CONCLUSIONS: Although high frequency ventilation reduces chronic lung disease, it seems to increase the risk of severe IVH. These results are dominated by an early study where the absence of benefit on pulmonary outcomes, and the increase in adverse neurological events, could be related to the low volume ventilatory strategy used. Recent studies, using a high lung volume approach, show better pulmonary outcomes without any increase in intracranial morbidity. Still, uncertainty remains about long term pulmonary and neurodevelopmental outcome. (+info)
Cranial magnetic resonance imaging and school performance in very low birth weight infants in adolescence.
(6/192)
AIM: To determine whether neurological deficits are associated with structural anomalies of the brain in very low birthweight (VLBW) infants with subsequent learning disorders but without cerebral palsy, or whether other factors, such as poor early growth, are responsible. METHODS: Eighty seven VLBW infants and eight term controls who had been examined at school between the ages of 12 and 13 years, had cranial magnetic resonance imaging (MRI) scans at 15-17 years of age. RESULTS: Thirty seven (42.5%) of the VLBW children had abnormalities reported on their scans (two porencephaly, 28 periventricular leucomalacia, 24 ventricular dilatation, and 15 thinning of the corpus callosum). No significant differences in intelligence quotient, motor clumsiness, or frequency of attention deficit / hyperactivity disorder were observed between those children with MRI lesions and those with normal scans. Quantitative measurements showed the VLBW infants had smaller brains, and a relatively smaller corpus callosum compared with controls. No association between brain measurements and school performance was observed among the VLBW infants. CONCLUSIONS: The difficulties experienced by VLBW children at school are unlikely to be the result of perinatal brain injury, but they might to be attributable to the effects of poor postnatal growth. (+info)
Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants.
(7/192)
BACKGROUND: Antenatal glucocorticoid therapy decreases the incidence of several complications among very premature infants. However, its effect on the occurrence of cystic periventricular leukomalacia, a major cause of cerebral palsy, remains unknown. METHODS: We retrospectively analyzed a cohort of 883 live-born infants, with gestational ages ranging from 24 to 31 weeks, who were born between January 1993 and December 1996 at three perinatal centers in the Paris area. The mothers of 361 infants had received betamethasone before delivery, the mothers of 165 infants had received dexamethasone before delivery, and the mothers of 357 infants did not receive glucocorticoids. We compared the rates of cystic periventricular leukomalacia among the three groups of infants in bivariate and multivariate analyses after adjustment for confounding factors. RESULTS: The rate of cystic periventricular leukomalacia was 4.4 percent among the infants whose mothers had received betamethasone, 11.0 percent among the infants whose mothers had received dexamethasone, and 8.4 percent among the infants whose mothers had not received a glucocorticoid. After adjustment for gestational age, the mode of delivery, and the presence or absence of chorioamnionitis, prolonged interval between the rupture of membranes and delivery (>24 hours), preeclampsia, and the use of tocolytic drugs, antenatal exposure to betamethasone was associated with a lower risk of cystic periventricular leukomalacia than was either the absence of glucocorticoid therapy (adjusted odds ratio, 0.5; 95 percent confidence interval, 0.2 to 0.9) or exposure to dexamethasone (adjusted odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). The adjusted odds ratio for the group of infants whose mothers had received dexamethasone as compared with the group of infants whose mothers had not received a glucocorticoid was 1.5 (95 percent confidence interval, 0.8 to 2.9). CONCLUSIONS: Antenatal exposure to betamethasone but not dexamethasone is associated with a decreased risk of cystic periventricular leukomalacia among very premature infants. (+info)
Correlation between magnetic resonance imaging and clinical profiles of periventricular leukomalacia.
(8/192)
Magnetic resonance imaging (MRI) findings of 70 children with periventricular leukomalacia (PVL), examined between 1 year 2 months and 8 years of age (mean: 2 years 4 months of age), were analysed. Neurological assessments were made between 1 year 3 months and 15 years (mean: 4 years 9 months). The possible correlations between MRI findings and clinical profiles of PVL were investigated using three parameters of the MRI findings. The grade of ventriculomegaly correlated well with the severity of cerebral palsy (CP) but not with the severity of mental impairment. The grade of reduction of periventricular white matter correlated well with the severity of CP and mental impairment, and is the most reliable parameter for neurological prognosis. The degree of periventricular hyperintensity on T2-weighted images did not correlate well with severity of CP, but correlated to some degree with mental impairment. There was a significantly lower degree of periventricular hyperintensity in children at less than 28 weeks of gestation than at 28 or more weeks of gestation, but no significant difference in other parameters. The periventricular hyperintensity should be evaluated in view of the gestational age. (+info)