Nina Mogridge

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.

Cognitive, educational, and behavioural outcomes at 7 to 8 years in a national very low birthweight cohort

AIMS To examine cognitive, behavioural, and educational outcomes in middle childhood among a birth cohort of very low birthweight children. METHODS Two hundred and ninety eight survivors from a national birth cohort of 413 New Zealand very low birthweight (VLBW) children born in 1986 were assessed at 7 to 8 years of age on measures of behaviour, cognitive ability, school performance and the need for special education. These outcomes were compared with the same measures in a general population sample of over 1000 children studied at a similar age. RESULTS The VLBW children had significantly higher rates of problems and poorer levels of functioning across all outcome measures than the general child sample. These differences persisted even after control for variability in social, family, and other characteristics of the two samples and for the degree of sensorineural disability. There was evidence of a gradient of risk with birthweight, with extremely low birthweight children having generally higher rates of problems and difficulties than other VLBW children after covariate control. CONCLUSIONS The findings are consistent with a growing body of research evidence which suggests that premature and VLBW infants are at increased risk of longer term morbidity and functional impairment in middle childhood.

Breast milk feeding and cognitive ability at 7-8 years

OBJECTIVE To examine the association between duration of breast milk feeding and cognitive ability at 7–8 years in a birth cohort of very low birthweight infants. DESIGN 280 survivors from a national birth cohort of 413 New Zealand very low birthweight infants born in 1986 were assessed at age 7–8 years on measures of verbal and performance intelligence quotient (IQ) using the WISC-R. At the same time mothers were questioned as to whether they had elected to provide expressed breast milk at birth and the total duration of breast milk feeding. RESULTS Some 73% of mothers provided expressed breast milk and 37% breast fed for four months or longer. Increasing duration of breast milk feeding was associated with increases in both verbal IQ (p < 0.001) and performance IQ (p < 0.05): children breast fed for eight months or longer had mean (SD) verbal IQ scores that were 10.2 (0.56) points higher and performance IQ scores that were 6.2 (0.35) points higher than children who did not receive breast milk. These differences were substantially reduced after control for selection factors associated with receipt of breast milk. Nevertheless, even after control for confounding, there remained a significant (p < 0.05) association between duration of breast milk feeding and verbal IQ: children breast fed for eight months or longer had adjusted mean (SD) verbal IQ scores that were 6 (0.36) points higher than the scores of those who did not receive breast milk. CONCLUSIONS These findings add to a growing body of evidence to suggest that breast milk feeding may have small long term benefits for child cognitive development.

Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome

Objective: To investigate the natural history and predictors of outcome of posthaemorrhagic ventriculomegaly in the very low birthweight (VLBW) infant. Methods: All VLBW infants admitted between September 1994 and September 1997 to the neonatal intensive care units of Brigham and Womens Hospital (Boston), Childrens Hospital (Boston), and Christchurch Womens Hospital (New Zealand) with germinal matrix intraventricular haemorrhage (IVH) were identified. All charts and ultrasound scans were reviewed to define the natural history and perinatal and/or postnatal factors of value in prediction of the course of posthaemorrhagic ventriculomegaly. Progressive ventricular dilatation (PVD) was defined from the results of serial cranial ultrasound scans. Results: A total of 248 VLBW infants had evidence of IVH (22% of all VLBW infants, mean (SD) gestational age 26.8 (2.6) weeks). A quarter of the infants exhibited PVD. Spontaneous arrest of PVD occurred without treatment in 38% of infants with PVD. Of the remaining 62% with persistent PVD, 48% received non-surgical treatment only (pharmacological and/or drainage of cerebrospinal fluid by serial lumbar punctures), 34% received surgical treatment with insertion of a ventriculoperitoneal reservoir and/or shunt, and 18% died. The development of PVD after IVH and adverse short term outcome, such as the requirement for surgery, were predicted most strongly by the severity of IVH. Conclusions: These data reflect the natural history of PVD in the 1990s and show that, despite a slight reduction in its overall incidence, there appears to be a more aggressive course, with appreciable mortality and morbidity in the extremely premature infant. The major predictor of adverse short term outcome, defined as death or need for surgical intervention, was the severity of IVH. These findings may be valuable for the management of very small premature infants.

3-Chlorotyrosine as a marker of protein damage by myeloperoxidase in tracheal aspirates from preterm infants: association with adverse respiratory outcome

Oxidative injury is implicated in the development of chronic lung disease in preterm infants with respiratory distress. However, direct evidence of a causal role is limited and the source of reactive oxidants has not been identified. We have previously shown that protein carbonyl levels in tracheal aspirates correlate positively with myeloperoxidase, suggesting that neutrophil oxidants could be the source of this protein injury. We have extended these observations by measuring 3-chlorotyrosine, a specific biomarker of the neutrophil oxidant, hypochlorous acid, in tracheal aspirate proteins (144 samples) from 69 infants with birth weight <1500 g. 3-Chlorotyrosine levels were higher in these infants than in larger infants without respiratory distress (median 83 compared with 13 μmol/mol tyrosine). They correlated strongly with myeloperoxidase activity (correlation coefficient 0.75, p < 0.0001) and to a lesser extent with protein carbonyls. 3-Chlorotyrosine levels (at 1 wk after birth) correlated negatively with birth weight or gestational age. They were significantly higher in infants who developed chronic lung disease (oxygen requirement at 36 wk postmenstrual age) than in those who did not (median 88 and 49 μmol/mol tyrosine, respectively) and correlated with days of supplemental oxygen. 3-Chlorotyrosine was also significantly higher in infants who had lung infection or were Ureaplasma urealyticum positive. Our results are the first evidence that chlorinated proteins are produced in the lungs of premature infants and that they are higher in infection. The higher 3-chlorotyrosine levels in infants who develop chronic lung disease suggest that neutrophil oxidants contribute to the pathology of this disease.

Protein Carbonyls and Lipid Peroxidation Products as Oxidation Markers in Preterm Infant Plasma: Associations with Chronic Lung Disease and Retinopathy and Effects of Selenium Supplementation

The purpose of this study was to determine whether protein carbonyls and the lipid peroxidation product malondialdehyde (MDA) are elevated in plasma from very low birth weight (<1500 g) infants, whether they are affected by selenium supplementation, and whether they are associated with poor respiratory outcome or retinopathy. The study group comprised 173 infants enrolled in a randomized controlled trial of selenium supplementation. Plasma samples, collected before randomization, at 7 and 28 d after birth, and at 36 wk postmenstrual age, were analyzed for protein carbonyls and total MDA. Respiratory outcome was assessed as oxygen requirement at 28 d of age or 36 wk postmenstrual age and as number of days on oxygen. Protein carbonyl concentrations in very low birth weight infants were significantly higher than for adults but lower than for cord blood from term infants. Median values decreased significantly by 28 d, and there was no relationship with birth weight. MDA concentrations in very low birth weight infants overlapped the ranges for healthy adults and cord blood from term infants. They correlated positively with birth weight at 28 d but not at other times. Supplementation almost doubled plasma selenium concentrations, but carbonyls and MDA did not differ between the supplemented and unsupplemented groups. There were no significant differences in oxidant marker levels in infants who did or did not develop chronic lung disease or retinopathy. Protein carbonyls and MDA measurements in plasma do not show evidence of systemic oxidative stress in <1500-g infants and are not affected by selenium supplementation. Oxidative injury at sites such as the lung may be important in prematurity, but markers from such sites must be measured to relate to outcome and antioxidant supplementation.

Selenium and Glutathione Peroxidase Levels in Premature Infants in a Low Selenium Community (Christchurch, New Zealand)

ABSTRACT: By world standards, the selenium status of the adult population of Christchurch, New Zealand is low. To determine the status of infants undergoing neonatal intensive care, plasma and red cell selenium and glutathione peroxidase levels were measured in infants admitted to the regional neonatal unit. Plasma levels in all newborn infants were one third to one half those in adults. Premature infants had levels significantly lower than those in cord blood from term infants, but their levels were not different from those of term infants admitted to the unit. There were no differences between adult and infant red cell levels. The premature infants remaining in the neonatal unit showed dramatic decreases in plasma selenium and glutathione peroxidase with age, with many infants having selenium levels of <0.13 μmol/L (10 μg/L). Low levels were seen in infants fed orally as well as those on parenteral nutrition. Thus, the low selenium status of New Zealanders is associated with particularly low selenium levels in premature infants. Because these infants have a high risk for oxidative diseases such as bronchopulmonary dysplasia (chronic lung disease) and retinopathy of prematurity, the possibility that these conditions are more serious in the New Zealand population needs to be assessed and consideration given to dietary supplementation.

Can neurobehavioral Examination predict the presence of cerebral injury in the very low birth weight infant

ABSTRACT. This study examined in a regional cohort of 66 term age very low birth weight infants, the relationship between qualitative magnetic resonance imaging (MRI) measures of cerebral white and gray matter abnormalities and infant neurobehavioral functioning assessed by structured neurological examination. The diagnostic utility of the Dubowitz neonatal neurological examination in identifying children with severe cerebral abnormalities was also evaluated. Examination results revealed the presence of high rates of neurological abnormality, with 60% of infants scoring in the suboptimal range relative to infants born full term. Linear associations were found between the severity of structural cerebral abnormality on MRI and the quality of clinically rated infant neurobehavioral functioning, with increasing abnormalities being significantly associated with poorer neurological functioning. In particular, white matter abnormalities were significantly associated with lower mean tone and tone pattern scores and a tendency toward lower mean reflex scores. Gray matter abnormalities were significantly associated with lower tone and tone pattern scores and a tendency toward lower spontaneous movements and orientation/behavior scores. Finally, the Dubowitz Neonatal Neurological Examination was found to have relatively good sensitivity (88%; negative predictive value, 92%) but poor specificity (46%; positive predictive value, 34%) for identifying children with significant MRI abnormalities. Implications of these findings for the neurological evaluation of the very low birth weight infant are discussed.

Very low birthweight and asthma by age seven years in a national cohort

Several studies have suggested that very low birthweight (VLBW < 1500 g) is associated with increased rates of respiratory problems in childhood and that the presence of chronic lung disease further increases the risk. We aimed to assess rates of asthma at 7–8 years of age in a national cohort of VLBW infants born in 1986 and for whom perinatal data were available. Two hundred ninety‐nine former VLBW children (96% of surviving children living in New Zealand) were assessed at a home visit. Parents were asked a comprehensive questionnaire, including three questions aimed at assessing morbidity from asthma: 1) was the child diagnosed as having asthma before age 7 years; 2) was the child still experiencing asthma at the age of 7 years; and 3) was the child prescribed daily medication for asthma at the age of 7 years.

Admissions of all gestations to a regional neonatal unit versus controls: 2‐year outcome

Aims:  To assess neurodevelopmental outcome at 2 years for neonatal intensive care unit (NICU) admissions compared with controls, and to trial a parent‐reporting scheme.