Placental pathology and outcome after perinatal asphyxia and therapeutic hypothermia.

OBJECTIVE: To assess the relationship between placental pathology, pattern of brain injury and neurodevelopmental outcome in term infants with perinatal asphyxia receiving therapeutic hypothermia. STUDY DESIGN: Studies were performed in 76 infants. Death or survival with impairments at 18 to 24 months was used as a composite adverse outcome. Multivariable analysis was performed. RESULTS: Among the 75 infants analyzed, the predominant pattern of brain injury was: no injury (n=27), a white matter/watershed pattern (n=14), basal-ganglia-thalamic injury (n=13) or near-total brain injury (n=21). An adverse outcome was seen in 35 of the 76 infants. Elevated nucleated red blood cells were associated with white matter involvement. Small placental infarcts were more common among infants without brain injury. All other placental abnormalities were not related to both outcome measures. CONCLUSION: In our population of term infants receiving therapeutic hypothermia, no type of placental pathology was related to extensive brain injury or adverse neurodevelopmental outcome.

Neonatal tract-based spatial statistics findings and outcome in preterm infants.

BACKGROUND AND PURPOSE: WM injury is associated with different disabilities that children born prematurely may experience during their lives. The aim of this study was to use TBSS to test the hypothesis that WM microstructure at TEA in preterm infants is correlated with cognitive and motor outcome at 2-year corrected age. MATERIALS AND METHODS: Sixty-three preterm infants, born at a mean gestational age of 28.7 weeks, underwent MR imaging and DTI at TEA. Neurodevelopmental performance was assessed by using the BSITD-III. Voxelwise analysis of the DTI data was performed by using TBSS to assess the relationship among FA, AD, and RD at TEA, and cognitive, fine-motor, and gross-motor scores at 2-year corrected age. RESULTS: Cognitive scores were correlated with FA values in the CC. Fine-motor scores were correlated with FA and RD throughout the WM. Gross-motor scores were associated with RD in the CC, fornix, and internal and external capsule. CONCLUSIONS: WM microstructure in preterm infants at TEA was associated with cognitive, fine-motor, and gross-motor performance at 2-year corrected age. This study suggests that TBSS of DTI data at TEA has the potential to be used as a biomarker for subsequent neurodevelopment.

Neurodevelopmental outcome over time of preterm born children ≤750 g at birth.

BACKGROUND: Extremely low birth weight (ELBW) infants are at risk of cognitive impairment and follow-up is therefore of major importance. The age at which their neurodevelopmental outcome (NDO) can reliably be predicted differs in the literature. AIMS: To describe NDO at 2, 3.5 and 5.5 years in an ELBW cohort. To examine the value of NDO at 2 years corrected age (CA) for prediction of NDO at 3.5 and 5.5 years. STUDY DESIGN: A retrospective cross-sectional and longitudinal cohort study. SUBJECTS: 101 children with a BW≤750 g, born between 1996 and 2005, who survived NICU admission and were included in a follow-up program. OUTCOME MEASURES: NDO, measured with different tests for general development and intelligence, depending on age of assessment and classified as normal (Z-score≥-1), mildly delayed (-2≤Z-score<-1) or severely delayed (Z-score<-2). RESULTS: At 2, 3.5 and 5.5 years 74.3, 82.2 and 76.2% had a normal NDO. A normal NDO at 2 years CA predicted a normal NDO at 3.5 and 5.5 years in 92% and 84% respectively. Of the children with a mildly or severely delayed NDO at 2 years CA the majority showed an improved NDO at 3.5 (69.2%) and 5.5 years (65.4%) respectively. CONCLUSIONS: The majority of the children with a BW≤750 g had a normal NDO at all ages. A normal NDO at 2 years CA is a good predictor for normal outcome at 3.5 and 5.5 years, whereas a delayed NDO at 2 years CA is subject to change with the majority of the children showing a better NDO at 3.5 and 5.5 years.

Symptomatic asymmetry in very young infants: a Delphi study on the development of a screening instrument.

The objective of this study was to develop a screening instrument for pediatric physiotherapists to distinguish a symptomatic asymmetry in the clinical evaluation of young infants (age <6 months) with an asymmetric head posture. We chose two consensus methods, a two-round Delphi design and an expert meeting using nominal group technique, for reaching agreement about classification of diagnoses and clinical diagnostic criteria (CDC). Seventeen diagnoses with an expression of asymmetry with 69 matching CDC were assessed. In two Delphi rounds, six medical specialists and seven pediatric physiotherapists were polled anonymously on the classification, completeness, and relevance of the diagnoses and the CDC. Panel consistency in round 2, expressed as Cronbach's-α, was 0.89. In round 3, a face-to-face meeting with eight therapists, the previously selected diagnoses and CDC were prioritised, reduced to 10 diagnoses and 21 CDC, and completed with eight hard clinical signs (red flags). Finally, a differential diagnostic screening instrument, containing a classification scheme, the CDC for differential diagnostics, and a list of "red flags" was established on the basis of literature search and expert consensus. Cross-validity and reliability of the instrument will be investigated in future research.

Two-year neurodevelopmental outcome of preterm born children ≤ 750 g at birth.

OBJECTIVES: To describe 2-year neurodevelopmental outcome (NDO) in a cohort of extremely low birthweight infants, and compare NDO between two consecutive 5-year periods and between appropriate (AGA, ≥p10) and small for gestational age (SGA, -1 Z score ≤-2) or severely delayed (Z score >-2). RESULTS: 74.3% of the children had a normal NDO at 2 years corrected age, 20.8% a mildly and 5% a severely delayed outcome. Although survival significantly increased with time (65.8% to 88.1%, p=0.002), significantly fewer children in cohort II (66.1% vs 84.4% in cohort I, p=0.042) as well as fewer SGA children (64.3% vs 86.7% of AGA children, p=0.012) had a normal NDO. CONCLUSIONS: Increased survival of infants with a birth weight ≤750 g coincided with more children with an impaired NDO at 2 years corrected age. SGA infants are especially at risk of impaired NDO.

Complications affecting preterm neonates from 1991 to 2006: what have we gained?

AIM: In this study, we determined whether outcome of preterm neonates has improved over a period of 16 years. STUDY DESIGN: Inborn neonates with a gestational age of 25.0-29.9 weeks were included. Patients with severe congenital malformations were excluded. Mortality and morbidity (chronic lung disease; CLD, intraventricular haemorrhage: IVH grade III or IV, cystic periventricular leukomalacia: cPVL, perforated necrotizing enterocolitis: NEC, severe retinopathy of prematurity needing surgery: ROP and cerebral palsy: CP) were compared in three periods (period 1: 1991-1996 n = 434; period 2: 1997-2001 n = 356; period 3: 2002-2006 n = 422). RESULTS: Infant mortality decreased from 15.2% to 10.9%. CLD did not differ significantly between periods (14.1-14.8%). Perforated NEC decreased from 2.8% to 1.6%. IVH grade III and IV both remained at 5.7% in period 3, whereas cPVL decreased significantly from 4.5% to 1.6%. Cerebral palsy decreased from 5.8% to 3.5% in period 3. Two neonates in each period were in need of surgery for ROP. CONCLUSION: Inborn preterm patients showed an improved survival and a significant reduction in cPVL and CP. Perforated NEC showed a trend to decrease. CLD and IVH grade III and IV remain a matter of concern.

Gross motor functional abilities in preterm-born children with cerebral palsy due to periventricular leukomalacia.

To describe the impact of periventricular leukomalacia (PVL) on gross motor function, data on 59 children (37 males, 22 females) with a gestational age (GA) of 34 weeks or less with cerebral palsy (CP) due to PVL grade I (n=20), II (n=13), III (n=25), and IV (n=1) were studied; (mean GA 29 wk 4d [SD 4 wk 6d]; mean birthweight 1318 g [SD 342]). Two independent raters used the Gross Motor Function Classification System (GMFCS) at four time points: T1, mean corrected age (CA) 9 months 15 days (SD 2 mo 6d); T2, mean CA 16 months (SD 1 mo 27 d); T3, mean CA 24 months 27 days (SD 2 mo 3d); and T4, median age 7 years 6 months (range 2 y 2 mo-16 y 8 mo). Interrater reliability and stability across time with respect to the total cohort were kappa>or=0.86 and rho>or=0.74 respectively. The association between PVL and gross motor outcome at T4 was strong (positive and negative predictive values 0.92 and 0.85 respectively). The proportion of children who remained in the same GMFCS level increased from 27% (T1-T4) to 53% (T2-T4) and 72% (T3-T4). PVL grade I to II, as diagnosed in the neonatal period, has a better functional mobility prognosis than PVL grade III-IV. These findings have implications for habilitation counselling and intervention strategies.

Early gross motor development of preterm infants according to the Alberta Infant Motor Scale.

OBJECTIVE: To systematically examine gross motor development in the first 18 months of life of preterm infants. STUDY DESIGN: A total of 800 preterm infants (356 boys), ages between 1 and 18 months and corrected for degree of prematurity, were assessed with the use of the Alberta Infant Motor Scale. RESULTS: Comparison of the mean Alberta Infant Motor Scale scores of the preterm infants with the norm-referenced values derived from term infants revealed that as a group, the preterm infants scored significantly lower at all age levels, even with full correction for degree of prematurity. CONCLUSIONS: In general, preterm infants exhibit different gross motor developmental trajectories compared with term infants in the first 18 months of life. The gross motor developmental profile of preterm infants may reflect a variant of typical gross motor development, which seems most likely to be specific for this population. As a consequence, adjusted norms should be used for proper evaluation and clinical decision-making in relation to preterm infants.

Neonatal cranial ultrasound versus MRI and neurodevelopmental outcome at school age in children born preterm.

AIM: To examine the correlation between neonatal cranial ultrasound and school age magnetic resonance imaging (MRI) and neurodevelopmental outcome. METHODS: In a prospective 2 year cohort study, 221 children (gestational age < or =32 weeks and/or birth weight < or =1500 g) participated at a median age of 8.1 years (inclusion percentage 78%). Conventional MRI, IQ (subtests of the WISC), and motor performance (Movement Assessment Battery for Children) at school age were primary outcome measurements. RESULTS: Overall, there was poor correspondence between ultrasound group classifications and MRI group classifications, except for the severe group (over 70% agreement). There was only a 1% chance of the children with a normal cranial ultrasound having a major lesion on MRI. Mean IQ (standard deviation) was significantly lower in children with major ultrasound or MRI lesions, but was also lower in children with minor lesions on MRI compared to children with a normal MRI (91+/-16, 100+/-13, 104+/-13 for major lesions, minor lesions, and normal MRI, respectively). Median total impairment score (TIS) was significantly higher in children with major lesions on ultrasound or MRI as well as in children with minor lesions on MRI (TIS 4.0 and 6.25 for normal and minor lesions on MRI, respectively; p<0.0001). CONCLUSIONS: A normal neonatal cranial ultrasound excluded a severe lesion on MRI in 99% of cases. MRI correlated more strongly with mean IQ and median TIS than ultrasound. Subtle white matter lesions are better detected with MRI which could explain the stronger correlation of MRI with IQ and motor performance.

Prediction of outcome in new-born infants with arterial ischaemic stroke using diffusion-weighted magnetic resonance imaging.

OBJECTIVE: The aim of this study was to assess the additional value of diffusion-weighted magnetic resonance imaging (DW-MRI) compared to conventional magnetic resonance imaging (MRI) in new-born infants with arterial ischaemic stroke, with regard to the prediction of neurodevelopmental outcome. METHODS: Neonatal DW-MRI data were available in 15 infants with a gestational age of > or = 35 weeks and repeat MRI data were obtained in 12 of the 14 survivors. T(1)- and T(2)-weighted transverse images were obtained as well as 4-mm DWI slices. ADC maps were calculated in manually selected regions on the basis of the DWI scans. All 14 survivors were seen in the follow-up clinic and 12 were > 18 months when last seen. RESULTS: T (2) hyperintensity was detected in the descending white matter tracts at the level of the internal capsule in 7 infants and in only one of these also at the level of the cerebral peduncles. Increased signal intensity (SI) was seen on DW-MRI in 8 infants in the descending white matter tract ipsilateral to the territorial infarct at the level of the internal capsule and in 5 of these also at the level of the cerebral peduncles. ADC maps were available in 12 infants. ADC values were calculated at the level of the cerebral peduncles, using the contralateral side as a reference value. A significantly reduced value was found in 3 of the 5 infants who showed an increased SI on DW-MRI. ADC maps were not available in the other two. Five of the seven infants with abnormalities on DW-MRI/ADC of the corticospinal tracts developed a mild to moderate hemiplegia, one showed an asymmetry of tone and one with only involvement of the anterior part of the internal capsule was normal at follow-up. Wallerian degeneration, seen at the level of the cerebral peduncles and/or the PLIC on the repeat MRI, was seen in the 5 infants who had shown acute changes of the corticospinal tracts in the neonatal period and who went on to develop motor sequelae. CONCLUSIONS: Compared to MRI, DW-MRI and ADC maps provided additional, quantitative data of acute corticospinal tract injury at an early time point after the insult, especially at the level of the cerebral peduncles. The presence of increased SI on DW-MRI at the level of the PLIC and the cerebral peduncles in new-born infants with arterial ischaemic stroke is followed by Wallerian degeneration and subsequent development of hemiplegia.

Larger corpus callosum size with better motor performance in prematurely born children.

The objective of this study is to determine the relation between the size of the corpus callosum (CC) and motor performance in a population-based cohort of preterm children. Preterm born children (n = 221) with a gestational age less than or equal to 32 weeks and/or a birth weight below 1500 g were eligible for this study. At the age of 7 or 8 years, frontal, middle, posterior, and total areas (mm2) of the corpus callosum were measured on true midsagittal MRI. Due to anxiety of 10 children and motion artifacts in 7 other children, 204 MRIs could be assessed in the preterm group (mean GA 29.4 weeks, sd 2.0,mean BW 1200 g, sd 323). The preterm group consisted of 15 children with cerebral palsy (CP) and 189 children without CP. Motor function was established by using the Movement Assessment Battery for Children, and the Developmental Test of Visual Motor Integration was obtained. The same examinations were performed in 21 term born children. The mean total cross-sectional CC area was significantly smaller in preterm born infants compared with their term born controls (338 mm2 versus 422 mm2, P < 0.0001). The preterm children with CP had significantly smaller mean CC areas compared with the preterms who did not develop CP (P < 0.0001-P < 0.002). However, the preterms born without CP also had significantly smaller body, posterior, and total CC areas compared with term born controls (P < 0.0001-P < 0.002). Only the difference in frontal area measurements dilrc) -3.3 mm2/score point (95% CI -4.5, -2.1). The association existed in all parts of the CC but increased in the direction of the posterior part: frontal: lrc -0.8 mm2/score point (-1.2, -0.4), middle: lrc -1.1 mm2/score point (-1.7, -0.5) and posterior: lrc -1.4 mm2/score point (-1.8, -0.9). An association between CC area and its subareas and the standard scores of the VMI was also found. A larger CC was strongly related t o better scores onthe VMI test total area CC: lrc 0.05 score/mm2 (95% CI 0.03, 0.07), frontal: lrc 0.12 score/mm2 (0.05,0.19), middle: lrc 0.10 score/mm2 (0.05, 0.15) and posterior: lrc 0.12 score/mm2 (0.06, 0.18). After adjustment for gestational age, birth weight, and total cerebral area, these associations were still significant. There is a strong association between the size of the corpus callosum (total midsagittal cross area as well as frontal, middle, and posterior area) and motor function in preterm children, investigated at school age. A poorer score on the Movement ABC was related to a smaller CC. A larger CC was strongly associated with better VMI standard scores.

Unilateral parenchymal haemorrhagic infarction in the preterm infant.

A unilateral parenchymal haemorrhage associated with a germinal matrix-intraventricular haemorrhage (GMH-IVH) is still an important problem in the preterm infant and especially in those who are very immature. This type of lesion is now considered mainly to be caused by impaired drainage of the veins in the periventricular white matter and is often referred to as a venous infarction. The risk factors and neonatal imaging findings, as well as neurodevelopmental outcome and imaging data in infancy, of this type of lesion differ from those found in children with bilateral periventricular leukomalacia. An effort should, therefore, always be made to make a distinction between these two types of lesions. In our experience it is possible to make this distinction in most cases, when performing both sequential ultrasonography as well as selective magnetic resonance imaging during the neonatal period.

Parenchymal brain injury in the preterm infant: comparison of cranial ultrasound, MRI and neurodevelopmental outcome.

AIM: Magnetic resonance imaging (MRI) is increasingly being used in high-risk preterm neonates. Cranial ultrasound (US) was compared with MRI in preterm patients with parenchymal injury and related to neurodevelopmental outcome. PATIENTS AND METHODS: Studies were performed in 61 patients. Twelve infants with normal US (Group 1) had an MRI within the first 4 weeks of life (early MRI), and 10 also at term age (late MRI). Eight out of 20 infants with intraventricular haemorrhage with parenchymal involvement (IVH + PI) (Group 2) had an early as well as a late MRI and 12 a late MRI. Of the 20 patients with cystic-periventricular leukomalacia (c-PVL) (Group 3), 7 had an early MRI, 1 had an MRI on both occasions and 12 had a late MRI. All 9 children with focal infarction (FI) (Group 4) had a late MRI. RESULTS: MRI was conform with cranial US in Group 1. Early MRI in Group 2 showed contralateral c-PVL in one infant and an additional contralateral occipital parenchymal haemorrhage and blood in the posterior fossa in another infant. Late MRI showed an asymmetrical posterior limb of the internal capsule (PLIC) (n=6), which predicted later hemiplegia. Early MRI in Group 3 showed more cysts (n = 5), punctate white matter lesions (n = 6), lesions in the basal ganglia (n = 1) and once involvement of the cerebellum. Late MRI showed involvement of the centrum semiovale (n = 2) lesions in the basal ganglia (n = 2) and bilateral abnormal signal intensity of the PLIC in 7 infants who all went on to develop cerebral palsy. In Group 4 MRI showed signal intensity changes suggestive of cystic lesions compared to persisting echogenicity on US (n = 3) and an asymmetrical PLIC (n = 5), which predicted hemiplegia in 4. CONCLUSION: Early MRI especially provided additional information in those with c-PVL. MRI at term age could assess the PLIC, which was useful in children with unilateral parenchymal involvement, for prediction of subsequent hemiplegia and, to a lesser degree, in bilateral c-PVL for prediction of diplegia or quadriplegia.

Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leucomalacia.

AIMS: To compare the ultrasound (US) evolution and neurodevelopmental outcome of infants with localised (grade II) and extensive (grade III) cystic periventricular leucomalacia (c-PVL). METHODS: Over a nine year period, c-PVL was diagnosed in 96/3451 (2.8%) infants in two hospital cohorts. Eighteen were excluded from the study. Thirty nine infants with grade II PVL were compared with 39 infants with grade III PVL. RESULTS: The two populations were comparable for gestational age and birth weight. In infants with grade II PVL, cysts were noted to develop more often after the first month of life (53%) in contrast with grade III PVL (22%) (odds ratio (OR) 3.81 (95% confidence interval (CI) 1.19 to 12.63)). Cysts were also more often unilateral in grade II (54%) than in grade III PVL (0%) (OR indefinite; RR 3.17 (95% CI 2.16 to 4.64)). At 40 weeks postmenstrual age (PMA), cysts were no longer seen on US in 13/38 infants with grade II PVL, with ventriculomegaly being the only visible sequel in nine cases. In grade III PVL, cysts were still present in 25 of the 27 surviving infants. Nine infants with grade II PVL were free of motor sequelae at follow up compared with one infant with grade III PVL (OR 8.07 (95% CI 0.92 to 181.66)). Twenty two out of 29 children with grade II PVL who developed cerebral palsy achieved independent walking compared with 3/26 with grade III PVL (OR 75 (95% CI 11.4 to 662)). CONCLUSIONS: In the cohort studied, 50% of the infants with c-PVL had a more localised form (grade II). In grade II PVL, the cysts developed beyond the first month of life in more than half of the cases and were often no longer visible, on US, at 40 weeks PMA. In order not to miss this diagnosis, sequential US should also be performed beyond the first month of life. Mild ventriculomegaly noted at term can sometimes be due to grade II c-PVL. Cerebral palsy was slightly less common and tended to be less severe in infants with grade II PVL than in those with grade III PVL.

Asymmetrical myelination of the posterior limb of the internal capsule in infants with periventricular haemorrhagic infarction: an early predictor of hemiplegia.

AIM: To prospectively assess the predictive value of asymmetrical myelination on MRI of the posterior limb of the internal capsule (PLIC) in newborn infants with an intraventricular haemorrhage (IVH) associated with unilateral haemorrhagic parenchymal involvement (PI), for subsequent development of a hemiplegia. METHODS: 12 preterm infants (GA 25-36 wks) and 4 full-term infants were studied. Using cranial ultrasound (US), the pre-term infants were diagnosed to have an IVH with unilateral PI. The term infants presented with a porencephalic cyst (PC) on the first postnatal US, following an antenatal IVH with PI. MRI was performed at 40 wks postmenstrual age in the pre-term infants and during the first 2 weeks of life in the full-term infants, using a 1.5T magnet. Using an inversion recovery sequence, the myelination of the internal capsule was recorded as normal, abnormal or equivocal. Neurological assessment > or = 12 months disclosed the presence of a hemiplegia or asymmetry in tone pattern. RESULTS: All 4 cases with a normal internal capsule had a normal outcome in spite of the development of a PC. All 9 cases with an abnormal PLIC developed a hemiplegia, while 1 of the 3 cases with an equivocal PLIC is normal on neurological assessment, one developed a mild asymmetry in tone and 1 a mild hemiplegia. CONCLUSION: While a symmetrical signal intensity within the internal capsule on MRI, performed at 40 weeks PMA, in infants with an IVH and unilateral PI appears to be strongly related to a normal outcome, an asymmetrical PLIC is an early predictor of future hemiplegia.

Correlation between neonatal cranial ultrasound, MRI in infancy and neurodevelopmental outcome in infants with a large intraventricular haemorrhage with or without unilateral parenchymal involvement.

UNLABELLED: During a 7-year-period, 1625 infants of 34 weeks gestation or less were enrolled in a prospective ultrasound (US) study. One hundred and eleven (6.8%) infants developed a large intraventricular haemorrhage (IVH) with or without unilateral parenchymal involvement (PI). Fifty-six of these 111 infants survived (50.4%) and in 23 (41%) of them a magnetic resonance imaging (MRI) study was performed beyond 12 months corrected age. There appeared to be a good agreement between neonatal ultrasound findings and MRI changes noted in infancy. Of the 10 cases with a large IVH without PI (group A), seven had a VP shunt with complete decompression of previously enlarged ventricles. Six of these seven infants had periventricular hyperintensity (PVHI) but none developed cerebral palsy (CP). Two of the ten cases without a VP shunt had irregular ventricular enlargement (VE) with PVHI in one. Both developed CP. Seven cases showed thinning of the corpus callosum. Of the 13 cases with a large IVH associated with PI (group B), the site of the PI could still be recognised on MRI and the degree of communication of the porencephalic cyst (PC) with the lateral ventricles correlated well with neonatal US findings. On MRI, VE was present in only 6 cases. Wallerian degeneration was present in 9/13 infants and all but one developed a hemiplegia. In 12/13 cases there was thinning of the corpus callosum, either focal or diffuse. PVHI was present in all infants. In 6/13 PVHI was only present around the PC. Neurodevelopmental outcome differed for both groups. CP was only present in 2/10 infants in group A, compared to 11/ 13 in group B. Global delay, in the absence of CP, was more common in infants with a large IVH than in those with associated PI. CONCLUSION: Combining neonatal US with MRI in infancy enhances our understanding of the long-term effects of severe haemorrhagic brain lesions, occurring in preterm infants.

Early cerebral proton MRS and neurodevelopmental outcome in infants with cystic leukomalacia.

The present study tested the hypothesis that proton magnetic resonance spectroscopy (1H-MRS) predicted neurodevelopmental outcome in infants with cystic leukomalacia (CL). Nineteen infants with CL (grade 2, N = 7; grade 3, N = 7; grade 4, N = 5), graded according to the authors' classification, were examined at corrected ages of mean 1.5 +/- 2.1 SD weeks. 1H-MRS of the basal ganglia and the periventricular white matter was performed. Two infants died, 16 had an adverse neurodevelopmental outcome and one was normal at follow-up. N-acetylaspartate (NAA):choline (Cho) ratios were mean 1.12 +/- 0.19 (SD) (grade 2), mean 0.95 +/- 0.11 (SD) (grade 3), and mean 0.71 +/- 0.13 (SD) (grade 4). These differences are significant (P < 0.01, ANOVA). NAA:Cho ratios showed a positive correlation with developmental quotient (DQ) at the age of > or = 1 year (P < 0.05). In 13 infants lactate (Lac) was found. Lac:NAA ratios showed a negative correlation with NAA:Cho ratios, but not with DQ. We conclude that a low NAA:Cho ratio predicted a poor outcome, whereas some infants developed unfavourably despite a normal NAA:Cho ratio. We speculate that partial volume effects might explain this observation.

Infarcts in the vascular distribution of the middle cerebral artery in preterm and fullterm infants.

Twenty-three infants with an infarct in the territory of the middle cerebral artery are reported. The diagnosis was made using cranial ultrasound in all, confirmed on postmortem in two cases and on MRI, performed during the neonatal period or in infancy, in 18 of the 20 survivors. Involvement of the main branch was present in 7 cases and three of these had a gestational age of less than 35 weeks. In the other 16 infants, involvement of a cortical branch or one or more of the lenticulostriate branches was present and all but three of these had a gestational age of 34 weeks or less. While involvement of the main branch was usually diagnosed on postnatal day 1 or 2 using ultrasound, involvement of the lenticulostriate branches was noted as a wedgeshaped echogenic lesion in the caudate nucleus, thalamus or putamen, between day 4 up till day 24, and at term age in one of the cases. Neurodevelopmental outcome of those with involvement of the main branch was disappointing as all survivors developed a hemiplegia, associated with epilepsy in two; while so far only three of the other 16 infants developed cerebral palsy, one a hemiplegia and one athetoid cerebral palsy. Global delay was present in a further three cases. Infarcts in the region of the middle cerebral artery can occur in both preterm as well as fullterm infants. Involvement of the main branch also occurred in infants with a gestational age below 35 weeks and resulted in the development of a hemiplegia in all survivors. Involvement of one of the other branches was especially common in preterm infants, who had a more favourable outcome. As the lesion in the latter group was usually not present before the end of the first week, serial ultrasound up till term age is needed in order to identify these lesions.

[Findings in cerebral proton spin resonance spectroscopy in newborn infants with asphyxia, and psychomotor development]. / Bevindingen bij cerebrale protonkernspinresonantie-spectroscopie bij pasgeborenen met asfyxie, en psychomotore ontwikkeling.

OBJECTIVE: To determine the relationship between the results of cerebral proton magnetic resonance spectroscopy (1H-MRS) and neuromotor development in neonates with hypoxia. DESIGN: Descriptive. SETTING: Wilhelmina Childrens' Hospital and University Hospital, Utrecht, The Netherlands. METHODS: 32 infants with hypoxic-ischaemic encephalopathy (Sarnat grade I (mild; n = 5), grade II (moderate; 20), grade III (severe; 7)) were examined at a mean of 8 days following the hypoxic event (range 2-22). 1H-MRS of the periventricular white matter and part of the basal ganglia was performed in a 1.5 T field: TR/TE: 2000/272 ms. Peak-to-peak NAA/Cho ratios were calculated. The presence of a lactate resonance was considered abnormal. Assessment of neuromotor development of the survivors was performed at 6, 9 and 18 months of age. RESULTS: 6 patients died (all grade III), 10 survived with handicaps (I grade III, 9 grade II). Handicaps consisted of spastic quadriplegia (n = 7), hemiplegia and mental retardation (n = 1), and global developmental delay (n = 2). The other 16 survivors were normal at 18 months. 1H-MRS showed NAA/Cho ratios of 0.97 (SD:0.13) in the patients with a normal outcome and 0.74 (0.17) in the patients with an adverse outcome (handicaps or death); p < 0.0001 (t-test). Lactate was demonstrated in all 7 grade III neonates, but not in any of the other infants. CONCLUSION: Cerebral 1H-MRS was related to neurodevelopmental outcome of neonates with HIE. A low NAA/Cho ratio and presence of a lactate resonance predicted an adverse outcome.

Correlation between the degree of periventricular leukomalacia diagnosed using cranial ultrasound and MRI later in infancy in children with cerebral palsy.

During a period of 30 months, 504 infants of 34 weeks gestation or less were enrolled in a prospective cranial ultrasound study. Ninety-two (18.4%) infants developed different degrees of periventricular leukomalacia (PVL), being transient periventricular echogenicities (PVE) in 75, localised cystic lesions in 7 and extensive cysts in 10. Eight of 75 (10.6%) infants with PVE, 4 of the 6 (66.6%) survivors with localised cysts and all 8 survivors with extensive cysts developed cerebral palsy in infancy and MRI studies could be performed in 15 of these 20 infants between 11 and 32 months of age. Neurological sequelae were most severe among the infants with extensive cysts and none were able to walk, while 6 of the 12 who developed cerebral palsy following either PVE or localised cysts had learned to walk independently. There appeared to be a good correlation between the degree of PVL, diagnosed using ultrasound, and the extent of MRI changes noted in infancy. Ventricular enlargement and delay in myelination were more common in infants with cystic lesions and periventricular hyperintensity (PVHI) was present in all infants, but most extensive in the cases with extensive cysts. MRI performed later in infancy may, even in the absence of neonatal cranial ultrasound, provide information about both the presence as well as the degree of leukomalacia, which the child may have suffered in the neonatal or antenatal period.