Can the Assessment of Spontaneous Oscillations by Near Infrared Spectrophotometry Predict Neurological Outcome of Preterm Infants?

The aim was to assess the correlation between cerebral autoregulation and outcome. Included were 31 preterm infants, gestational age 26 1/7 to 32 2/7 and <24 h life. Coherence between cerebral total haemoglobin (tHb) or oxygenation index (OI) measured by near-infrared spectrophotometry (NIRS) and systemic heart rate (HR) or arterial blood pressure (MAP) was calculated as a measure of autoregulation. In contrast to previous studies, low coherences in the first 24 h were significantly associated with intraventricular haemorrhage, death or abnormal neurodevelopmental outcome at 18 months or later. We suggest that our results can be explained by the concept of a multi-oscillatory-functions-order.

Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter development in preterm infants.

Despite improved survival, many preterm infants undergo subsequent neurodevelopmental impairment. To date, no neuroprotective therapies have been implemented into clinical practice. Erythropoietin, a haematopoietic cytokine used for treatment of anaemia of prematurity, has been shown to have neuroprotective and neuroregenerative effects on the brain in many experimental studies. The aim of the study was to assess the effect of recombinant human erythropoietin on the microstructural development of the cerebral white matter using tract-based spatial statistics performed at term equivalent age. A randomized, double-blind placebo-controlled, prospective multicentre study applying recombinant human erythropoietin in the first 42 h after preterm birth entitled 'Does erythropoietin improve outcome in preterm infant' was conducted in Switzerland (NCT00413946). Preterm infants were given recombinant human erythropoietin (3000 IU) or an equivalent volume of placebo (NaCl 0.9%) intravenously before 3 h of age after birth, at 12-18 h and at 36-42 h after birth. High resolution diffusion tensor imaging was obtained at 3 T in 58 preterm infants with mean (standard deviation) gestational age at birth 29.75 (1.44) weeks, and at scanning at 41.1 (2.09) weeks. Imaging was performed at a single centre. Voxel-wise statistical analysis of the fractional anisotropy data was carried out using tract-based spatial statistics to test for differences in fractional anisotropy between infants treated with recombinant human erythropoietin and placebo using a general linear model, covarying for the gestational age at birth and the corrected gestational age at the time of the scan. Preterm infants treated with recombinant human erythropoietin demonstrated increased fractional anisotropy in the genu and splenium of the corpus callosum, the anterior and posterior limbs of the internal capsule, and the corticospinal tract bilaterally. Mean fractional anisotropy was significantly higher in preterm infants treated with recombinant human erythropoietin than in those treated with placebo (P < 0.001). We conclude that early recombinant human erythropoietin administration improves white matter development in preterm infants assessed by diffusion tensor imaging and tract-based spatial statistics.

Development of neuromotor functions in very low birth weight children from six to 10 years of age: patterns of change.

AIM: To assess patterns of change for different neuromotor functions in very low birth weight (VLBW) children during school age and to identify factors associated with improvement. METHODS: In a longitudinal study, we examined 65 prospectively enrolled VLBW children (38 female, 59%) without cerebral palsy at age six and 10 years. Measures included the evaluation of timed motor performance and motor overflow (MO) for the motor components of the Zurich Neuromotor Assessment (pure motor-, adaptive fine- and gross motor tasks, static balance) and a standardized neurological examination. Variables associated with improvement were assessed by multiple regression analyses. RESULTS: Between six and 10 years, adaptive fine motor tasks (40% vs. 17% of children scoring below 10th percentile) and MO (77% vs. 55%) improved significantly (both p<0.01), while all other components remained stable (pure motor 23% vs. 25%, adaptive gross motor 26% vs. 34%, static balance 18% vs. 20%, respectively). Mild neurological abnormalities at 6 years of age were associated with less improvement. CONCLUSION: Neuromotor functions improve in some children potentially reflecting catch up of maturational delay. However, the majority of neuromotor functions remain abnormal in a significant proportion of VLBW children.

Health-related quality of life and behavior of triplets at adolescent age.

OBJECTIVES: To assess health-related quality of life (HRQoL) and behavior of triplets compared with matched singletons at adolescent age and to identify medical and sociodemographic predictors of outcome. STUDY DESIGN: Fifty-four triplets (19 sets, mean [SD] gestational age 32.0 [2.4] weeks, birth weight 1580 [450] g) and 51 gestational age-, birth weight-, and sex-matched singleton controls self-rated their HRQoL at age 14.5 (0.3) years. Proxy reports about HRQoL and behavior were obtained by parents and teachers. HRQoL was measured with the Kidscreen-52 questionnaire child and parent form, and behavior with the Achenbach Child Behavior Checklist. RESULTS: Self- and parent-reported HRQoL values was similar in both groups except for the dimensions "mood and emotions" and "autonomy," which were better (P = .001, P = .03) in triplets. Parents reported significantly less behavioral problems in triplets compared with controls. Compared with community norms, both HRQoL and behavior measures in triplets were in the normal range. Parent-reported HRQoL was predicted by dichorionicity. CONCLUSIONS: HRQoL and behavioral outcome in adolescent triplets was good in our study and was, in some aspects, better than in matched singleton controls. Dichorionicity is an important outcome determinant.

The role of birthweight discordance in the intellectual and motor outcome for triplets at early school age.

AIM: We assessed motor and intellectual outcome in triplets at school age and investigated the predictive value of perinatal and demographic factors. METHODS: Seventy-one live-born newborn infants (24 triplet pregnancies) were prospectively enrolled at birth. At the age of 6 years, 58 children (31 males, 27 females; mean gestational age 31.2 wks [SD 2.2 wks]; mean birthweight 1622 g [SD 440 g]) returned for a neurodevelopmental examination. A comparison group for triplets born before 32 gestational weeks comprising 26 gestational age-, birthweight-, and sex-matched singletons was also recruited (mean gestational age 30.1 wk [SD 1.5 wk]; mean birthweight 1142 g [SD 210 g]; 12 males, 14 females). The Zurich Neuromotor Assessment was used to examine motor performance, and intellectual abilities were assessed with the Kaufman Assessment Battery for Children (K-ABC). RESULTS: Motor performance and movement quality in these individuals was significantly reduced compared with the test norms for all motor tasks (p<0.001) other than static balance. The mean values on the Mental Processing Composite (95.3, SD 8.4) and the Achievement Scale (90.1, SD 13.8) of the K-ABC were also lower than those in the test reference (p<0.05 and p<0.01 respectively). Triplets born at less than 32 weeks' gestation showed poorer pure motor and adaptive gross motor performance (both p<0.05) than, but similar intellectual performance to, the gestational age-, birthweight- and sex-matched singletons. Poor outcome was predicted by low socio-economic status and by intertriplet birthweight discordance (both p<0.01). INTERPRETATION: Triplets were at an increased risk of mild motor and intellectual impairments. This finding is important for tailoring therapeutic interventions for these children and for parental counselling. Very preterm triplets showed similar outcomes to the singleton comparison children, except that they had poorer motor performance. Low socio-economic status was a major risk factor for impaired intellectual development. In addition, birthweight discordance may also be considered a predictor for poor long-term motor and intellectual outcome in triplets.

Impaired motor performance and movement quality in very-low-birthweight children at 6 years of age.

Motor performance and movement quality were quantitatively examined (Zurich Neuromotor Assessment: timed motor performances and associated movements) in 87 prospectively enrolled very-low-birthweight (VLBW; <1250g) children (38 males, 49 females; mean birthweight 1016.2g [SD 141.5]:, range 720-1240g; mean gestational age 28.7wks [SD 2], range 25.7-33.4wks) at 6 years of age. All motor tasks were below the reference population: pure motor (median z-score) -0.46; adaptive fine motor (pegboard) -0.99; adaptive gross motor -0.88; static balance -0.48; and associated movements -1.90. All tasks correlated with the degree of neurological abnormalities (p

Improved outcome for very low birth weight multiple births.

This study describes time trends for very low birth weight multiple births in relation to very low birth weight singletons. Two cohorts of very low birth weight (less than 1250 gm) children recruited between 1983-85 (cohort 1, n = 115) and 1992-94 (cohort 2, n = 144) were compared. The Bayley Scales of Infant Development and a standardized neurologic examination were administered at 2 years corrected age. Neurodevelopmental outcome did not change between cohort 1 and 2 for singletons. For multiple births, mean Mental Developmental Index increased after adjustment for neonatal risk factors [adjusted mean (standard deviation) 81.8 (11.7) to 96.5 (18.6), analysis of covariance P = 0.007]. The prevalence of cerebral palsy decreased, however not significantly [adjusted odds ratio (95% confidence interval) 0.3 (0.1-1.5), P = 0.14]. The proportion of disease-free survival (no cerebral palsy and no developmental delay) increased for multiple births (7-37%, P = 0.002), but not for singletons. In cohort 2, neurodevelopmental outcome of multiple births was similar to that of singletons. The cognitive outcome of very low birth weight multiple births improved, possibly because of changes in perinatal practice. However, neurodevelopmental outcome was similar to that of very low birth weight singletons who were unaffected by changes in neonatal care with high proportions of motor delay and cerebral palsy.

Variability of cerebral hemoglobin concentration in very preterm infants during the first 6 hours of life.

Cerebral hemoglobin concentration (cHbc), a major determinant of oxygen transport capacity in the brain, shows a considerable variability due to physiological and methodological factors. In order to determine the (relative) contribution of these factors, the cHbc variability within the first 6 hours of life was studied in 28 very preterm infants using near infrared spectrophotometry (NIRS). Mean cHbc values were 46.4 +/- 14.1 micromol/l (2.75 +/- 0.84 ml/100 g). Is the variability in cHbc related to the methodology of cHbc measurements or to physiological variables? A statistical model of stepwise regression (backward selection) with 13 independent variables and with cHbc as a dependent variable showed that, from the total variability of +/- 14.1 micromol/l, only 3.7 micromol/l (26%) were of methodological origin, while the major portion, 9.3 micromol/l (66%) were related to four physiological variables: birth weight, gestational age, blood glucose and transcutaneous carbon dioxide tension. The remaining 1.1 micromol/l (7.8%) were unexplained. We conclude that NIRS, which allows continuous monitoring of cerebral oxygenation and metabolism even in the first hours of postnatal life, is a valid technique to measure cHbc in very preterm infants. The major portion of the large variability of early cHbc registrations can be attributed to physiological factors.

Tissue oxygenation monitoring during major pediatric surgery using transcutaneous liver near infrared spectroscopy.

BACKGROUND: The aim of the study was to compare liver tissue oxygenation determined by near infrared spectroscopy (NIRS) with central venous oxygen saturation (SvO(2)) and intestinal perfusion as measured by gastric intramucosal pH (pHi) in pediatric surgical patients. METHODS: Twenty children undergoing craniofacial surgery with expected major intraoperative blood loss were studied. NIRS tissue oxygenation index (TOI(Liver)) and pHi values were recorded. Arterial blood gas analysis and SvO(2) were assessed from periodically taken blood samples. Data are presented as ranges (median) and were compared using linear regression analysis. Sensitivity and specificity of the intra-individual changes in TOI(Liver) to predict falling SvO(2) or pHi values were calculated. RESULTS: Patients age ranged from 0.79 to 8.27 years (1.92 years). TOI(Liver) ranged from 41.5 to 77.4% (61.5%), gastric pHi from 7.13 to 7.60 (7.37) and SvO(2) from 51 to 86% (74%). Among patients only moderate correlation was found between TOI(Liver) and SvO(2) (r = 0.594, P < 0.0001) and gastric pH(i) (r = 0.502, P < 0.0001). Intra-individual measured TOI(Liver) values, however, demonstrated close correlation with SvO(2) values (r = 0.680 to 0.976) but a varying correlation with gastric pHi values (r = 0.055 to 0.972). Sensitivity/specificity of TOI(Liver) to predict decreasing SvO(2) or gastric pHi values were 76.4/73.4% and 67.4/62.7% respectively. CONCLUSIONS: TOI(Liver) provided a better trend monitor of central venous oxygen saturation than gastric intramucosal pH. Because of its limited sensitivity and specificity to indicate deterioration of SvO(2), liver tissue oxygenation measured by transcutaneous NIRS does not provide additional practical information for clinical management.

Postnatal growth in VLBW infants: significant association with neurodevelopmental outcome.

OBJECTIVE: To study the significance of growth status at birth and postnatal growth on neurodevelopmental outcome in very low birth weight (VLBW) infants. STUDY DESIGN: Growth and neurodevelopment were examined in 219 VLBW (<1250 g) children, 94 small for gestational age (SGA) (<10th percentile) and 125 appropriate for gestational age (AGA) (>10th percentile). Outcome at age 2 was assessed with the Bayley Scales of Infant Development (Mental Developmental Index [MDI], Psychomotor Developmental Index [PDI]) and a standardized neurologic examination. RESULTS: SGA status was not associated with poor neurodevelopmental outcome. However, after adjustment for covariables including cerebral palsy (CP), SGA children with weight <10th percentile at age 2 had lower mean PDI than SGA children with catch-up growth to weight >10th percentile (mean [SD], 89.9 [17.4] versus 101.8 [14.5]; P<.001). AGA children with catch-down growth (weight <10th percentile at age 2) were, independent of CP, more likely to have lower mean MDI (94.9 vs 101.7, P=.05) and PDI (81.9 vs 95.1; P<.001) than AGA children remaining >10th percentile at age 2. They also more frequently had severe CP (22.9% vs 1.2%; P=.008). CONCLUSIONS: In VLBW children, the course of postnatal growth rather than the appropriateness of weight for gestational age at birth determines later neurodevelopmental outcome.