Carole Spencer

Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study.

Abstract Objectives The aim of this study was to define qualitatively the nature and extent of white and gray matter abnormalities in a longitudinal population-based study of infants with very low birth weight. Perinatal factors were then related to the presence and severity of magnetic resonance imaging (MRI) abnormalities. Methods From November 1998 to December 2000, 100 consecutive premature infants admitted to the neonatal intensive care unit at Christchurch Womens Hospital were recruited (98% eligible) after informed parental consent to undergo an MRI scan at term equivalent. The scans were analyzed by a single neuroradiologist experienced in pediatric MRI, with a second independent scoring of the MRI using a combination of criteria for white matter (cysts, signal abnormality, loss of volume, ventriculomegaly, corpus callosal thinning, myelination) and gray matter (gray matter signal abnormality, gyration, subarachnoid space). Results were analyzed against individual item scores as well as the presence of moderate-severe white matter score, total gray matter score, and total brain score. Results The mean gestational age was 27.9±2.4 weeks (range, 23-32 weeks), and mean birth weight was 1063±292 g. The greatest univariate predictors for moderate-severe white matter abnormality were lower gestational age (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.7; P P P =0.03), inotropic support (OR, 2.7; 95% CI, 1.5-4.5; P P =.01), grade III/IV intraventricular hemorrhage ( P =.015), and the occurrence of a pneumothorax ( P =.05). There was a significant protective effect of intrauterine growth restriction (OR, 0.51; 95% CI, 0.23-0.99; P =.04). Gray matter abnormality was highly related to the presence and severity of white matter abnormality. A unique pattern of cerebral abnormality consisting of significant diffuse white matter atrophy, ventriculomegaly, immature gyral development, and enlarged subarachnoid space was found in 10 of 11 infants with birth gestation Conclusions This MRI study confirms a high incidence of cerebral white matter abnormality at term in an unselected population of premature infants, which is predominantly a result of noncystic injury in the extremely immature infant. We confirm that the major perinatal risk factors for white matter abnormality are related to perinatal infection, particularly maternal fever and infant sepsis, and hypotension with inotrope use. We have defined a distinct pattern of diffuse white and gray matter abnormality in the extremely immature infant.

Elevated Free Radical Products in the Cerebrospinal Fluid of VLBW Infants with Cerebral White Matter Injury

Free radical mediated cellular injury has been hypothesized to play a key role in the pathogenesis of white matter injury in the premature infant, although direct evidence is lacking. Between April 1999 and May 2001, 22 very low birthweight infants, 30 term infants, and 17 adults had samples of cerebrospinal fluid (CSF) collected for clinical indications. Only CSF samples without any evidence of meningeal inflammation were analyzed for the levels of the lipid peroxidation products, 8-isoprostane and malondialdehyde (MDA), and protein carbonyls as a measure of protein oxidation. Chlorotyrosine was monitored as a measure of neutrophil oxidative activity. In the premature infants with subsequent evidence of white matter injury on magnetic resonance imaging at term, there was a significant elevation in the CSF level of protein carbonyls in comparison with the level in healthy premature infants, term infants, and adult controls (all p < 0.001). A significant difference in the levels of the lipid peroxidation products, 8-isoprostane and MDA, was apparent between premature infants with white matter injury and adult controls (isoprostanes p = 0.02, MDA p = 0.014). There was a trend toward higher levels of 8-isoprostane in the premature infants with white matter injury in comparison with those without white matter injury (p = 0.08), with 5 of the 14 infants with white matter injury having levels that were more than 10-fold higher than the top of the adult range. There was no significant difference in the level of chlorotyrosines among any of the groups. These preliminary data provide evidence of an association of elevated oxidative products during the evolution of white matter injury in the human premature infant.

Very preterm birth: maternal experiences of the neonatal intensive care environment

Objective:Examine sources, predictors and child outcomes associated with neonatal intensive care unit (NICU)-related stress for mothers of infants born very preterm (VPT).Study Design:Participants were 133 mothers of VPT infants admitted to a regional level-III NICU. At term equivalent, mothers completed the Parental Stressor Scale: NICU and were interviewed about their psychological well-being and family circumstances. Infant clinical data were also collected. At corrected age 4 years, 49 children were assessed for cognition, language and socio-emotional development.Result:Mothers reported moderate to low stress, with parental role alteration considered most stressful and parent–staff communications least stressful. Predictors of overall stress included maternal educational underachievement, stressful life events, postnatal depression and infant unsettled-irregular behavior. NICU-related stress was associated with child anxiety and poorer language development.Conclusion:Parental well-being is an important focus of care in the neonatal setting. Strategies are needed to optimize early engagement and reduce stress levels to assist improved child outcomes.

Health service utilisation of a regional cohort of very preterm infants over the first 2 years of life.

Aim:  Very preterm infants represent major consumers of health services following neonatal discharge. We examined the health service utilisation of a regional cohort of very preterm infants over the first 2 years of life, including the association with neurodevelopmental outcome.

Psychosocial characteristics and poly-drug use of pregnant women enrolled in methadone maintenance treatment.

Pregnant women with substance dependency are a high-risk psychiatric and obstetric population, with their infants also at elevated neonatal risk. This paper draws on prospective, longitudinal data from a regional cohort of 81 methadone-maintained (MM) and 107 comparison women and their infants to describe the obstetric, socio-familial and mental health needs of women in methadone maintenance treatment during pregnancy. Of particular interest was the extent and pattern of maternal licit and illicit drug use over the course of pregnancy. Results showed that MM women had complex reproductive histories, chronic health problems, and were subject to high rates of socioeconomic adversity and comorbid mental health problems. During pregnancy, more than half continued to use licit and illicit drugs, although there was a general trend for drug use to reduce over time. No differences were observed between women maintained on low (12.5-61.0mg/day) and high (61.1-195.0mg/day) doses of methadone, with the exception of opiate abuse which was higher in the low dose group (p=.07). Findings highlight that pregnant women enrolled in MMT and their infants represent a vulnerable group with complex, social, obstetric and psychiatric needs. They also reinforce the need for services that can provide on-going wrap-around, multidisciplinary and multiagency care for these high risk dyads, both during pregnancy and in the transition to parenthood.

Defining the nature of the cerebral abnormalities in the premature infant: A qualitative magnetic resonance imaging study

OBJECTIVES The aim of this study was to define qualitatively the nature and extent of white and gray matter abnormalities in a longitudinal population-based study of infants with very low birth weight. Perinatal factors were then related to the presence and severity of magnetic resonance imaging (MRI) abnormalities. METHODS From November 1998 to December 2000, 100 consecutive premature infants admitted to the neonatal intensive care unit at Christchurch Womens Hospital were recruited (98% eligible) after informed parental consent to undergo an MRI scan at term equivalent. The scans were analyzed by a single neuroradiologist experienced in pediatric MRI, with a second independent scoring of the MRI using a combination of criteria for white matter (cysts, signal abnormality, loss of volume, ventriculomegaly, corpus callosal thinning, myelination) and gray matter (gray matter signal abnormality, gyration, subarachnoid space). Results were analyzed against individual item scores as well as the presence of moderate-severe white matter score, total gray matter score, and total brain score. RESULTS The mean gestational age was 27.9+/-2.4 weeks (range, 23-32 weeks), and mean birth weight was 1063+/-292 g. The greatest univariate predictors for moderate-severe white matter abnormality were lower gestational age (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.7; P<.01), maternal fever (OR, 2.2; 95% CI, 1.1-4.6; P<.04), proven sepsis in the infant at delivery (OR, 1.8; 95% CI, 1.1-3.6; P=0.03), inotropic support (OR, 2.7; 95% CI, 1.5-4.5; P<.001), patent ductus arteriosus (OR, 2.2; 95% CI, 1.2-3.8; P=.01), grade III/IV intraventricular hemorrhage (P=.015), and the occurrence of a pneumothorax (P=.05). There was a significant protective effect of intrauterine growth restriction (OR, 0.51; 95% CI, 0.23-0.99; P=.04). Gray matter abnormality was highly related to the presence and severity of white matter abnormality. A unique pattern of cerebral abnormality consisting of significant diffuse white matter atrophy, ventriculomegaly, immature gyral development, and enlarged subarachnoid space was found in 10 of 11 infants with birth gestation <26 weeks. Given the later outcome of these infants, this pattern may have very high risk for later global neurodevelopmental disability. CONCLUSIONS This MRI study confirms a high incidence of cerebral white matter abnormality at term in an unselected population of premature infants, which is predominantly a result of noncystic injury in the extremely immature infant. We confirm that the major perinatal risk factors for white matter abnormality are related to perinatal infection, particularly maternal fever and infant sepsis, and hypotension with inotrope use. We have defined a distinct pattern of diffuse white and gray matter abnormality in the extremely immature infant.