Admission of all gestations to a regional neonatal unit versus controls: neonatal morbidity.

AIMS: To describe the neonatal course and morbidity of all infants admitted to the regional neonatal intensive care unit (NICU) at Christchurch Women's Hospital (CWH) and to compare these with term control infants who were not admitted, in one calendar year. Infants in both NICU and control cohorts were enrolled in a 2-year follow-up study. METHODS: All infants born over a 12-month period from February 2001 and admitted to the NICU, whose parents were domiciled in a defined geographical region, were eligible for study, together with every eighth healthy infant born at term and not admitted (to a total of 300). Comprehensive perinatal and neonatal data were collected for all enrolled infants. RESULTS: A total of 387 NICU infants (86% eligible) were enrolled in the study together with 306 controls. Forty-one percent of NICU admissions were term and 40% were 33-36 weeks gestation. Term NICU infants were more likely to be born following induction of labour or by Caesarean section (34%, of which 50% were pre-labour) than control infants (18%, of which 32% were pre-labour). Infants of <28, 28-32, 33-36 and > or =37 weeks accounted for 74, 16, 7 and 3% of assisted ventilation days and 18, 31, 31 and 20% of total baby days, respectively. CONCLUSIONS: The need for assisted ventilation and length of NICU stay was inversely proportional to gestation. However, preterm infants of 28 weeks gestation and greater, as well as term infants, account for a high proportion of the NICU workload.

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. METHODS: All infants admitted to the NICU at Christchurch Women's Hospital over a 12-month period and whose parents were domiciled in a defined geographical region were eligible for study, together with every eighth term infant not admitted (to a total of 300). Parents completed a two-page questionnaire on their child's 2nd birthday. All infants <28 weeks gestation and a random 300 NICU admissions and 108 controls underwent a paediatric examination and Bayley II assessment at 2 years of age. RESULTS: A total of 387 NICU infants (86% eligible) and 306 controls were enrolled. At 2 years of age, 276 NICU infants (89% survivors) and 94 controls (87%) had some follow up. For infants of <33 weeks, 33-36 weeks, > or =37 weeks gestation and controls, the percentage >1 SD below the mean on the Bayley Mental Development Index scales were 33.3, 36.5, 44.6 and 24.1, respectively (P= 0.03); on the Psychomotor Developmental Index scales were 30.0, 29.1, 41.1 and 19.5 (P= 0.02) and the percentage with any cerebral palsy were 11.1, 2.8, 5.2 and 1.2. CONCLUSIONS: At 2 years of age, NICU graduates have more developmental problems than controls across a range of measures. In many cases, term NICU graduates have the least favourable outcome. There was only moderate agreement between parents' reporting of moderate or severe developmental disability by means of a questionnaire, compared with professionals (kappa statistic 0.38), with parents tending to underestimate problems.

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

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.

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 Women's 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.

Fetal renal pelvic dilatation--poor predictor of familial vesicoureteral reflux.

The sensitivity and positive predictive value (PPV) of fetal renal pelvic dilatation for detecting vesicoureteral reflux (VUR) can only be determined by performing voiding cystourethrography (VCUG) on all newborns in a study population. We sought to determine this for infants with a family history of reflux. From June 1989 to September 1996, 157 children (80 males) under 2 years with a family history of primary VUR in a first-degree relative had VCUG. VCUG results were compared with the fetal renal pelvic diameter on obstetric sonogram performed after 16 weeks gestation. Of the 157 infants, 33 (11 boys) had primary VUR. In those with a parent as the index case, the prevalence of reflux was 5% in boys and 35% in girls ( P=0.03). The largest renal pelvic diameter after 16 weeks was not discriminatory for VUR, but after 30 weeks gestation a 4 mm renal pelvis had a sensitivity of 33% and a PPV of 32%. The sensitivity was higher for grades 4 and 5 (75%) than for grades 1-3 reflux (17%), ( P=0.04). In conclusion, fetal renal pelvic diameter has a low sensitivity and poor predictive value for detecting VUR, but this improves a little after 30 weeks gestation.

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 micromol/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 micromol/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.