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Cerebellar hemorrhage (CBH) is a frequent complication of preterm birth and may play an important and under-recognized role in neurodevelopment outcome. Association between CBH size, location, and neurodevelopment is still unknown. The main objective of this study was to investigate neurodevelopmental outcome at 2 years of age in a large number of infants with different patterns of CBH. Of preterm infants (≤ 34 weeks) with known CBH, perinatal factors, neuro-imaging findings, and follow-up at 2 years of age were retrospectively collected. MRI scans were reassessed to determine the exact size, number, and location of CBH. CBH was divided into three groups: punctate (≤ 4 mm), limited (> 4 mm but < 1/3 of the cerebellar hemisphere), or massive (≥ 1/3 of the cerebellar hemisphere). Associations between pattern of CBH, perinatal factors, and (composite) neurodevelopmental outcome were assessed. Data of 218 preterm infants with CBH were analyzed. Of 177 infants, the composite outcome score could be obtained. Forty-eight out of 119 infants (40%) with punctate CBH, 18 out of 35 infants (51%) with limited CBH, and 18 out of 23 infants (78%) with massive CBH had an abnormal composite outcome score. No significant differences were found for the composite outcome between punctate and limited CBH (P = 0.42). The risk of an abnormal outcome increased with increasing size of CBH. Infants with limited CBH have a more favorable outcome than infants with massive CBH. It is therefore important to distinguish between limited and massive CBH.

Although bilateral injury to the thalami is often seen in (near)term infants with hypoxic ischemic encephalopathy (HIE), symmetrical thalamic lesions (STL) is a different, very rare condition, seen both in full-term and preterm infants often after an antenatal insult, although the history is not always clear. These lesions are usually first detected using cranial ultrasound (cUS). They may not always be seen on the first (admission) scan, but become apparent in the course of the 1st week after birth. Clinically, these infants present with hypo- or hypertonia, absence of sucking and swallowing reflexes, and they may have contractures and facial diplegia. Neuropathology commonly demonstrates a thalamic lesion with additional and variable involvement of basal ganglia and brainstem. The prognosis is very poor, the condition often leads to severe disabilities and/or death within the first years of life. The clinical course and neuroimaging findings of 13 patients with symmetrical thalamic lesions (STL) are reported., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI., Study Design: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis., Results: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03)., Conclusions: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation., Trial Registration: ISRCTN43171322., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Punctate white matter lesions (PWMLs) are small focal patches of increased signal intensity (SI) on T1- and decreased SI on T2-weighted magnetic resonance imaging (MRI). To date, there have been few reports of PWMLs in term born infants., Objective: To identify associated diagnoses and factors predictive of clinical outcome in (near) term infants with PWMLs., Methods: MRI studies and clinical records of (near) term infants, with PWMLs on MRI scans performed in two institutions in the first 28 postnatal days were reviewed. The PWMLs were classified according to their number, pattern and distribution. The medical records were examined to assess the associated diagnoses and determine the neurodevelopmental outcome at >12 months of age. Infants with congenital heart defect(s), those who had neonatal surgery, or those with perinatal arterial ischemic stroke were not eligible for the study., Results: Forty-two (near) term infants with PWMLs were included. The major clinical association was perinatal asphyxia, present in 19/42 (45%). Ten (24%) had a history of seizures unrelated to asphyxia or a genetic diagnosis. Eleven (26%) had pathological genetic mutations. Other diagnoses, without seizures were identified in 2 (5%). The lesion load of PWMLs was high (>6) in 30/42 (71%). Evidence of irreversible white matter injury was present in 5 infants who had follow-up MRI performed between 18 and 24 months of age, because of clinical concerns. Five infants died and 37 had follow-up at a median age of 24 months. Neurodevelopmental outcome was poorest amongst 6 infants (16%) whose PWMLs occurred in the setting of a genetic disorder., Conclusion: PWMLs in (near) term infants represent white matter injury that may evolve into gliosis and/or white matter loss. Infants with PWMLs in the setting of a genetic disorder appeared at most risk of a poor outcome., (Copyright © 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare a low versus a higher threshold for intervention in preterm infants with posthaemorrhagic ventricular dilatation., Design: Multicentre randomised controlled trial (ISRCTN43171322)., Setting: 14 neonatal intensive care units in six countries., Patients: 126 preterm infants ≤34 weeks gestation with ventricular dilatation after grade III-IV haemorrhage were randomised to low threshold (LT) (ventricular index (VI) >p97 and anterior horn width (AHW) >6 mm) or higher threshold (HT) (VI>p97+4 mm and AHW >10 mm)., Intervention: Cerebrospinal fluid tapping by lumbar punctures (LPs) (max 3), followed by taps from a ventricular reservoir, to reduce VI, and eventually a ventriculoperitoneal (VP) shunt if stabilisation of the VI below the p97+4 mm did not occur., Composite Main Outcome Measure: VP shunt or death., Results: 19 of 64 (30%) LT infants and 23 of 62 (37%) HT infants were shunted or died (P=0.45). A VP shunt was inserted in 12/64 (19%) in the LT and 14/62 (23%) infants in the HT group. 7/12 (58%) LT infants and 1/14 (7%) HT infants required shunt revision (P<0.01). 62 of 64 (97%) LT infants and 36 of 62 (58%) HT infants had LPs (P<0.001). Reservoirs were inserted in 40 of 64 (62%) LT infants and 27 of 62 (43%) HT infants (P<0.05)., Conclusions: There was no significant difference in the primary composite outcome of VP shunt placement or death in infants with posthaemorrhagic ventricular dilatation who were treated at a lower versus a higher threshold for intervention. Infants treated at the lower threshold received more invasive procedures. Assessment of neurodevelopmental outcomes will provide further important information in assessing the risks and benefits of the two treatment approaches., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an "early approach" (EA), based on ventricular measurements exceeding normal (ventricular index [VI] <+2 SD/anterior horn width <6 mm) with initial temporizing procedures, followed, if needed, by permanent shunt placement, and a "late approach" (LA), based on signs of increased intracranial pressure with mostly immediate permanent intervention., Methods: Observational cohort study of 127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or LA (n = 49). Ventricular size was measured on cranial ultrasound. Outcome was assessed at 18-24 months., Results: Forty-nine of 78 (63%) EA and 24 of 49 (49%) LA infants received intervention. LA infants were slightly younger at birth, but did not differ from EA infants for other clinical measures. Initial intervention in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p < 0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted predominantly of lumbar punctures or reservoir taps. Maximum VI in infants with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p < 0.001) and complications were lower in EA than LA group. Most EA infants had normal outcomes (>-1 SD), despite intervention. LA infants with intervention had poorer outcomes than those without ( p < 0.003), with scores <-2 SD in 81%., Conclusion: In preterm infants with PHVD, those with early intervention, even when eventually requiring a shunt, had outcomes indistinguishable from those without intervention, all being within the normal range. In contrast, in infants managed with LA, need for intervention predicted worse outcomes. Benefits of EA appear to outweigh potential risks., Classification of Evidence: This study provides Class III evidence that for preterm infants with PHVD, an EA to management results in better neurodevelopmental outcomes than a LA., (© 2018 American Academy of Neurology.)

Background: Despite advances in neonatal intensive care, germinal matrix-intraventricular hemorrhage (GMH-IVH) remains a frequent, serious complication of premature birth. Neutral head position and head tilting have been suggested to reduce the risk of GMH-IVH in preterm infants during the first 72 h of life., Objective: The aim of this study was to provide a systematic review of the effect of neutral head positioning and head tilting on the incidence of GMH-IVH in very preterm infants (gestational age ≤30 weeks). In addition, we reviewed their effect on cerebral hemodynamics and oxygenation., Methods: Literature was searched (June 2016) in the following electronic databases: CINAHL, Embase, Medline, SCOPUS, and several trial registers., Results: One underpowered trial studied the effect of head positioning on the incidence of GMH-IVH. This randomized controlled trial enrolled 48 preterm infants and found no effect on the occurrence of GMH-IVH. Three observational studies investigated the effect of head rotation and/or tilting on cerebral oxygenation in 68 preterm infants in total. Their results suggest that cerebral oxygenation is not significantly affected by changes in head positioning. The effect of head positioning and/or tilting on cerebral hemodynamics was described in 2 observational studies of 28 preterm infants and found no significant effect., Conclusions: There is insufficient evidence regarding the effect of head positioning and tilting on the incidence of GMH-IVH and cerebral hemodynamics and oxygenation in preterm infants. We recommend further research in this field, especially in extremely preterm and clinically unstable infants during the first postnatal days., (© 2016 S. Karger AG, Basel.)

Cranial ultrasonography (CUS) is a reliable and non-invasive tool to detect frequently occurring brain abnormalities and to monitor brain development and maturation in high risk neonates. Standard CUS views are obtained through the anterior fontanel. However, evaluation of the posterior fossa is often suboptimal with this approach. Cerebellar injury occurs frequently in preterm infants and has important prognostic consequences. Early detection is therefore important. This review focuses on techniques that optimize the performance of CUS when studying the preterm cerebellum, including the use of the mastoid fontanel and the adaptation of focus points and scan frequencies. For illustration, CUS images of the normal posterior fossa anatomy as well as examples of abnormalities that may be encountered in preterm infants are included. We also discuss the limitations of CUS and the role of magnetic resonance imaging., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare autosomal recessive bone marrow failure, caused by MPL gene mutations. The combination of CAMT and central nervous system abnormalities is uncommon. We describe a case with a homozygous missense MPL gene mutation and polymicrogyria, underdevelopment of the cerebellum, and multiple intracranial hemorrhages., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: We aimed to assess the characteristics of posterior fossa (PF) abnormalities in a cohort of high-risk term neonates, as well as the diagnostic performance of cranial ultrasound (CUS) with additional mastoid fontanelle (MF) views for the detection of these abnormalities, with magnetic resonance imaging (MRI) being the reference standard., Methods: In this retrospective study, 113 term neonates with CUS and subsequent MRI were included. Sensitivity, specificity, and predictive values of routine CUS and CUS with MF views were calculated., Results: Posterior fossa abnormalities were diagnosed on CUS in 46 of 113 infants. MRI confirmed these findings in 43 and showed additional abnormalities in 32 infants. The sensitivity and specificity of anterior fontanelle views for major PF abnormalities as seen on MRI were 16% and 99%. Adding MF views increased the sensitivity of US to 82%. The sensitivity and specificity of MF views for the detection of any (major or minor) PF abnormality were 57% and 95%. Especially acute hypoxic-ischemic injury and small subdural and punctate cerebellar haemorrhage remained undetected by CUS., Conclusions: PF abnormalities are frequent in high-risk term infants. MF-CUS enables early diagnosis of major PF abnormalities. We therefore advocate to perform MF-CUS in high-risk term neonates., Key Points: • Posterior fossa abnormalities are a frequent finding in high-risk term infants. • Adding mastoid fontanelle views improves ultrasound detection of clinically relevant abnormalities. • Hypoxic-ischemic injury and small posterior fossa haemorrhages are better detected with MRI. • Cranial ultrasound examination should include mastoid fontanelle views in high-risk term neonates.

Background: Gradient echo T2*-W sequences are more sensitive than T2-W spin-echo sequences for detecting hemorrhages in the brain., Objective: The aim of this study is to correlate presence of hemosiderin deposits in the brain of very preterm infants (gestational age <32 weeks) detected by T2*-W gradient echo MRI to white matter injury and neurodevelopmental outcome at 2 years., Materials and Methods: In 101 preterm infants, presence and location of hemosiderin were assessed on T2*-W gradient echo MRI performed around term-equivalent age (range: 40-60 weeks). White matter injury was defined as the presence of >6 non-hemorrhagic punctate white matter lesions (PWML), cysts and/or ventricular dilatation. Six infants with post-hemorrhagic ventricular dilatation detected by US in the neonatal period were excluded. Infants were seen for follow-up at 2 years. Univariate and regression analysis assessed the relation between presence and location of hemosiderin, white matter injury and neurodevelopmental outcome., Results: In 38/95 (40%) of the infants, hemosiderin was detected. Twenty percent (19/95) of the infants were lost to follow-up. There was a correlation between hemosiderin in the ventricular wall with >6 PWML (P < 0.001) and cysts (P < 0.001) at term-equivalent age, and with a lower psychomotor development index (PDI) (P=0.02) at 2 years. After correcting for known confounders (gestational age, gender, intrauterine growth retardation and white matter injury), the correlation with PDI was no longer significant., Conclusion: The clinical importance of detecting small hemosiderin deposits is limited as there is no independent association with neurodevelopmental outcome.

The objective of the study is to determine perinatal and postnatal factors that may affect the occurrence of small cerebellar hemorrhage (CBH) and to evaluate the effect of small CBH on neurodevelopmental outcome in very preterm infants. This prospective study in an unselected cohort of very preterm infants was approved by the medical ethics committee, and informed parental consent was obtained. Presence of small CBH (<4 mm) was assessed with magnetic resonance imaging around term equivalent age in 108 preterm infants (<32 weeks gestation). We compared infants with and without small CBH for perinatal and postnatal factors, supratentorial brain injury, and for neurodevelopmental outcome at 2 years corrected age. Follow-up consisted of a neurological examination, mental and developmental assessment (Bayley Scales of Infant Development), and behavior checklist. Univariate and multivariate logistic regression analyses were performed to examine the relationships between variables. Small CBH was diagnosed in 16/108 very preterm infants. Univariate analyses identified gestational age, high-frequency oscillation (HFO) ventilation, and grade 3-4 intraventricular hemorrhage (IVH) as factors associated with small CBH. HFO ventilation and severe IVH were independent predictors of small CBH. We found no association between small CBH and neurodevelopmental outcome at 2 years of age. Small CBH is a frequent finding in preterm infants. These hemorrhages are independently associated with HFO ventilation and severe supratentorial hemorrhage and seem to have a favorable short-term prognosis.

Objective: To asses the relation between echogenicity changes in the fetal brain and neurodevelopmental outcome until 6 years of age., Methods: Fetuses (n = 124) from pregnancies affected by hypertensive disorders (n = 64) or preterm labor (n = 60) at risk for preterm birth (26-34 weeks gestation) were studied. Moderate echogenicity changes (periventricular grade IB, II; intraventricular grade II-III; local basal ganglia/thalami) in the fetal and neonatal brain were related to neurological outcome and Griffiths mental developmental scales quotients at 1, 2 and 6 years. Multiple regression analysis tested the influence of moderate echogenicity changes and perinatal clinical characteristics on composite outcome (death or abnormal neurodevelopment)., Results: Moderate echogenicity changes were present in 37/124 (30%) fetuses. Median gestational age and weight at birth were respectively 31 weeks (range 26-43), 1314 g (range 550-4330), mortality was 19%, follow-up loss 10%. Composite outcome was abnormal in 47/124 (38%). Fetal and neonatal moderate intraventricular echodensities were related to cerebral palsy at 6 years (p < 0.04). In the multiple regression analysis only gestational age was related to composite outcome (p = 0.005)., Conclusions: Moderate intraventricular echodensities in the fetal brain related to cerebral palsy at 6 years of age. Gestational age at birth was the main predictor of abnormal composite outcome.

Aim: The aim of this study was to determine whether tractography of white-matter tracts can independently predict neurodevelopmental outcome in very preterm infants., Method: Out of 84 very preterm infants admitted to a neonatal intensive care unit, 64 (41 males, 23 females; median gestational age 29.1 weeks [range 25.6-31.9]; birthweight 1163 g [range 585-1960]) underwent follow-up at 2 years. Diffusion tensor imaging (DTI) values obtained around term were associated with a neurological examination and mental and psychomotor developmental index scores at 2 years based on the Bayley Scales of Infant Development (version 3). Univariate and logistic regression analyses tested for associations between DTI values and follow-up parameters. Cut-off values predicting motor delay and cerebral palsy (CP) were determined for fractional anisotropy, apparent diffusion coefficient (ADC), and fibre lengths., Results: Infants with psychomotor delay and CP had significantly lower fractional anisotropy values (p=0.002, p=0.04 respectively) and shorter fibre lengths (p=0.02, p=0.02 respectively) of the posterior limb of the internal capsule. Infants with psychomotor delay also had significantly higher ADC values (p=0.03) and shorter fibre lengths (p=0.002) of the callosal splenium. Fractional anisotropy values of the posterior limb of the internal capsule independently predicted motor delay and CP, with sensitivity between 80 and 100% and specificity between 66 and 69%. ADC values of the splenium independently predicted motor delay with sensitivity of 100% and specificity of 65%., Interpretation: Diffusion tensor imaging tractography at term-equivalent age independently predicts psychomotor delay at 2 years of age in preterm infants., (© The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.)

Background: The main causes of severe fetal anaemia are red-cell allo-immunization, parvo B19 virus infection and feto-maternal haemorrhage. Treatment consists of intrauterine transfusion (IUT). Neuro-imaging studies in surviving neonates treated with IUT are scarce., Aims: To assess if neonates treated with IUT for fetal anaemia are at risk for cerebral injury, report the incidence and severity of brain ultrasound (US) abnormalities and explore the relation between brain US findings and perinatal parameters and neurological outcome., Patients and Methods: Brain US scans of neonates born alive between 2001 and 2008 with at least one IUT were retrospectively reviewed and classified as normal, mildly or moderately/severely abnormal. Incidences of abnormalities were calculated for full-term and preterm neonates. Presence and severity of abnormalities were related to clinical and IUT related parameters and to neurological outcome around 2 years of age (adverse: moderate or severe disability; favourable: normal or mild disability)., Results: A total of 127 neonates (82 born preterm) were included. Median number of IUTs was 3 (range 1-6) and of brain US 2 (1-6). Median gestational age and weight at birth were 36.6 (26.0-41.1) weeks and 2870 (1040-3950)g. In 72/127 (57%) neonates ≥1 abnormality was seen on brain US, classified as moderate/severe in 30/127 (24%). Neurological outcome was adverse in 5 infants. Presence of brain US abnormalities was not significantly related to any of the perinatal parameters or to neurological outcome., Conclusions: Neonates undergoing IUT for fetal anaemia are at high risk of brain injury., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Routine cranial ultrasonography, using the anterior fontanelle as acoustic window enables visualization of the supratentorial brain structures in neonates and young infants. The mastoid fontanelle enables a better view of the infratentorial structures, especially cerebellar hemorrhage in preterm infants. Reports on the usefulness and reliability of cranial ultrasonography using the mastoid fontanelle approach for the detection of posterior fossa abnormalities, focusing only on full-term neonates are limited. This article describes the technique of mastoid fontanelle ultrasonography in full-term neonates and the features of posterior fossa abnormalities that may be encountered in various neonatal disorders and conditions, combined with subsequent MRI in the same patients. Cranial ultrasound through the mastoid fontanelle plays a pivotal role in the early detection of posterior fossa pathology and selection of neonates with an indication for MRI., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: To explore the association between diffuse excessive high signal intensity (DEHSI), punctate white matter (WM) lesions, and ventricular dilatation around term-equivalent age (TEA) and at clinical follow-up at 2 years in very preterm infants and the effect on neurodevelopment., Materials and Methods: Ethical approval for this prospective study was given by the institutional review board, and informed parental consent was obtained. An unselected cohort of 110 preterm infants (gestational age, < 32 weeks) was imaged around or after TEA. Clinical follow-up was performed at a corrected age of 2 years and consisted of a neurologic examination and a mental and developmental assessment (Bayley Scales of Infant Development). Univariate analyses and logistic and linear regression were performed to examine the relationships between variables., Results: DEHSI was found in 58 of 65 (89%) infants imaged around TEA. DEHSI was never detected in infants imaged after postmenstrual age of 50 weeks and showed no association with neurodevelopmental outcome. Punctate WM lesions and ventricular dilatation were significantly associated with mental (P = .02 for punctate WM lesions) and psychomotor developmental delay (P < .001 and P = .03, respectively), motor delay (P = .002 and P = .02, respectively), and cerebral palsy (P = .01 and P = .03, respectively)., Conclusion: Because of its high incidence in preterm infants around TEA, its absence after a postmenstrual age of 50 weeks, and its association with normal neurologic outcome at a corrected age of 2 years, DEHSI should not be considered part of the spectrum of WM injury, but rather a prematurity-related developmental phenomenon., (© RSNA, 2011.)

Aim: Diffuse white matter injury is not well detected by cranial ultrasonography (CUS). The aim of this study was twofold: (1) to assess in very preterm neonates the predictive values of individual CUS abnormalities for white matter injury on MRI and neurological outcome; (2) to develop a strategy optimizing CUS detection of white matter injury., Method: Very preterm neonates (n=67; 44 males, 23 females) underwent serial CUS and single MRI. Predictive values of CUS findings for a white matter classification on MRI, individual MRI findings, and neurological outcome at 2 years corrected age were calculated. The effects of timing and frequency of CUS were evaluated., Results: Periventricular echodensities (PVEs) predicted abnormal white matter on MRI, but absence of PVEs did not predict absence of white matter changes. Peri- and intraventricular haemorrhage (P/IVH) was highly predictive of abnormal white matter on MRI. Frequency and timing of CUS did not influence predictive values. P/IVH and abnormal ventricular size/shape were reasonably predictive of unfavourable outcome, whereas absence of CUS abnormalities predicted a favorable outcome., Interpretation: (1) If PVEs are present, there is a significant chance of abnormal white matter on MRI. (2) Increasing frequency of CUS does not increase its diagnostic performance for white matter injury. (3) P/IVH is highly predictive of abnormal white matter on MRI and reasonably predictive of unfavourable outcome. (4) Absence of PVEs and P/IVH on CUS does not guarantee normal white matter, but predicts a favourable outcome., (© The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.)

Objectives: To investigate in preterm infants associations between Diffusion Tensor Imaging (DTI) parameters of the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) and age, white matter (WM) injury and clinical factors., Methods: In 84 preterm infants DTI was performed between 40-62 weeks postmenstrual age on 3 T MR. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) values and fibre lengths through the PLIC and the genu and splenium were determined. WM injury was categorised as normal/mildly, moderately and severely abnormal. Associations between DTI parameters and age, WM injury and clinical factors were analysed., Results: A positive association existed between FA and age at imaging for fibres through the PLIC (r = 0.48 p < 0.001) and splenium (r = 0.24 p < 0.01). A negative association existed between ADC and age at imaging for fibres through the PLIC (r = -0.65 p < 0.001), splenium (r = -0.35 p < 0.001) and genu (r = -0.53 p < 0.001). No association was found between DTI parameters and gestational age, degree of WM injury or categorical clinical factors., Conclusions: These results indicate that in our cohort of very preterm infants, at this young age, the development of the PLIC and CC is ongoing and independent of the degree of prematurity or WM injury.

Purpose: To elucidate whether echogenicity (EG) of the basal ganglia and thalami (BGT) represents a physiologic phenomenon in preterm neonates (<32 weeks gestation)., Materials and Methods: The study was approved by the medical ethics committee, and informed consent was obtained from the parents. Sequential neonatal cranial ultrasonographic (US) images obtained in 130 preterm neonates were evaluated for EG of the BGT. In 110 of the 130 neonates, MR imaging was performed around or within the first months after term-equivalent age to assess myelination and changes in BGT signal. Cranial US studies obtained in 83 low-risk near-term neonates were used for comparison., Results: Diffuse homogeneous bilateral EG of the BGT was seen in 120 (92%) of 130 preterm neonates and in seven (8%) of 83 low-risk neonates (P < .001). In preterm neonates, EG of the BGT faded with age and was no longer seen 1 month after delivery. This finding was associated with frontal echodensity, which is a normal prematurity-related cranial US phenomenon that occurs in the white matter (P < .001). No association with changes on MR images was found., Conclusion: In preterm neonates, diffuse homogeneous EG of the BGT is a frequent and normal prematurity-related finding., (© RSNA, 2011.)

Background: Chronic hypoxia and inflammatory processes can induce placental disturbances that may indirectly lead to perinatal brain injury., Objective: To study histological features of the placenta in relation to echogenicity changes in the periventricular white matter, ventricular system and basal ganglia/thalami of the fetal brain., Design: Prospective study of 77 fetuses between 26 and 34 weeks gestational age with their placentas. The pregnancies were complicated by hypertensive disorders (n=42) or preterm labour (n=35)., Results: Of the placentas 79% showed uteroplacental hypoperfusion, inflammation or a combination. Transvaginal ultrasound examination of the brain revealed echogenicity changes in 73% of the fetuses (44 mild, 29 moderate). Moderate brain echogenicity changes (periventricular echodensity (PVE) grade IB: increased echogenicity brighter than choroid plexus, intraventricular echodensity (IVE) grade II and III: echodensity filling ventricle respectively <50% and ≥50%; basal ganglia/thalamic echodensity (BGTE): locally increased echogenicity within basal ganglia/thalami) were equally distributed over cases with uteroplacental hypoperfusion and inflammatory features in the placenta. PVE grade IB was always associated with placental pathology. The sensitivity and negative predictive value of placental pathology for moderate echogenicity changes were high (0.91 and 0.88, respectively), while the specificity and positive predictive value were low (0.27 and 0.34, respectively)., Conclusions: Normal placental histology predicted no or mild echogenicity changes, supporting the view that the latter are physiological. Placental pathology was always present in cases with grade IB PVE, presumed to represent mild or early forms of white matter injury. Both uteroplacental hypoperfusion and inflammatory features were seen in placentas from pregnancies with hypertensive disorders.

Background and Purpose: Cerebral sinovenous thrombosis is a rare disease with severe neurological sequelae. The aim of this retrospective multicenter study was to investigate the clinical course, possible risk factors, and outcome of a cohort of neonatal patients with sinovenous thrombosis and, second, to estimate the incidence in The Netherlands., Methods: From January 1999 to March 2009, a review of all neonatal patients with sinovenous thrombosis from 6 tertiary neonatal intensive care units was performed. Population characteristics, clinical presentation, (prothrombotic) risk factors, neuroimaging, interventions, and neurodevelopment were evaluated. An estimated incidence was calculated based on the Netherlands Perinatal Registry., Results: Fifty-two neonates were included (39 boys) with a median gestational age of 39 weeks (range, 30 to 42 weeks; 5 preterm). An assisted or complicated delivery occurred in 32 of 52. Presenting symptoms developed at a median postnatal age of 1.5 days (range, 0 to 28 days) and consisted mainly of seizures (29 of 52). All sinovenous thrombosis cases were confirmed with MRI/MR venography. Multisinus thrombosis was most common followed by superior sagittal sinus thrombosis. FII G20210A mutation was present in 2 of 18 tested neonates (11%). Anticoagulation therapy (in 22 of 52) did not result in hemorrhagic complications. At follow-up (median age, 19 months; range, 3 to 72 months), moderate to severe neurological sequelae were present in 38%. The mortality was 10 of 52 (19%). A variable, although high yearly incidence of 1.4 to 12 per 100 000 term newborns was found., Conclusions: Neonatal sinovenous thrombosis is a multifactorial disease. The estimated incidence in The Netherlands seems higher than reported elsewhere.

Introduction: Cranial ultrasound (cUS) may not be reliable for detection of diffuse white matter (WM) injury. Our aim was to assess in very preterm infants the reliability of a classification system for WM injury on sequential cUS throughout the neonatal period, using magnetic resonance imaging (MRI) as reference standard., Methods: In 110 very preterm infants (gestational age <32 weeks), serial cUS during admission (median 8, range 4-22) and again around term equivalent age (TEA) and a single MRI around TEA were performed. cUS during admission were assessed for presence of WM changes, and contemporaneous cUS and MRI around TEA additionally for abnormality of lateral ventricles. Sequential cUS (from birth up to TEA) and MRI were classified as normal/mildly abnormal, moderately abnormal, or severely abnormal, based on a combination of findings of the WM and lateral ventricles. Predictive values of the cUS classification were calculated., Results: Sequential cUS were classified as normal/mildly abnormal, moderately abnormal, and severely abnormal in, respectively, 22%, 65%, and 13% of infants and MRI in, respectively, 30%, 52%, and 18%. The positive predictive value of the cUS classification for the MRI classification was high for severely abnormal WM (0.79) but lower for normal/mildly abnormal (0.67) and moderately abnormal (0.64) WM., Conclusion: Sequential cUS during the neonatal period detects severely abnormal WM in very preterm infants but is less reliable for mildly and moderately abnormal WM. MRI around TEA seems needed to reliably detect WM injury in very preterm infants.

Background: In preterm born infants abnormal general movements (GMs) generally normalize before three months post term, but may persist when perinatal brain injury is present., Aims: To assess the continuity of GM quality from fetal to early neonatal period and its relation to brain echogenicity changes., Study Design: Prospective study examining GMs and three vulnerable brain areas before and 7days after birth. The quality of GMs was classified as normal or abnormal by Gestalt-perception. The brain was examined for moderate echogenicity changes (periventricular: brighter than choroid plexus, intraventricular: filling equal or more than 50% of the ventricle, and locally increased basal ganglia/thalami)., Subjects: 94 fetuses from pregnancies complicated by preterm hypertensive disorders or labour at a gestational age between 26 and 34weeks., Outcomes Measures: Correlations of fetal GMs, echogenicity changes, and clinical parameters (e.g. gestational age, parity, hypertensive disorders or preterm labour, oligohydramnios and fetal growth restriction) with neonatal GMs., Results: Fetal GMs were abnormal in 64%, normalizing in 68% within 7days after birth. Fetal GMs were significantly related to postnatal GMs (p=0.045). Moderate fetal brain echogenicity changes and clinical parameters were not significantly related to neonatal GM., Conclusions: In this population of pregnancies compromised by hypertensive disorders or preterm labour fetal GMs correlated with neonatal GMs. Presence of moderate echogenicity changes in the fetal brain was not related to neonatal GMs.

In experienced hands, cranial ultrasonography (cUS) is an excellent tool to detect the most frequently occurring brain abnormalities in preterm and full-term neonates, to study the evolution of lesions, and to follow brain maturation. It enables screening of the brain and serial imaging in high-risk neonates. However, cUS also has limitations and magnetic resonance imaging is needed in most neonates with (suspected) parenchymal brain injury and/or neurological symptoms and in very preterm infants. In this review, we discuss the applications, possibilities, indications, predictive value, and limitations of neonatal cUS. We will pay attention to the standard cUS procedure and expand on optimizing the possibilities of cUS by using supplemental acoustic windows and changing transducers and focus points. For illustration numerous cUS images are provided., ((c) 2010 Elsevier Inc. All rights reserved.)

Purpose: To investigate the incidence and characteristics of cerebellar injury in a cohort of very preterm infants by using the mastoid fontanelle (MF) and posterior fontanelle (PF) approach in addition to routine cranial ultrasonography (US) through the anterior fontanelle (AF), with magnetic resonance (MR) imaging as the reference standard., Materials and Methods: The institutional review board approved this prospective study and informed consent was obtained. A cohort of 77 preterm infants (< 32 weeks) was examined with serial cranial US throughout the neonatal period by using the AF, PF, and MF views. MR imaging was performed around term-equivalent age in 59 of 77 infants. Sensitivity, specificity, positive predictive value, and negative predictive value of routine cranial US and cranial US with additional views were calculated., Results: At cranial US performed through the MF, seven (9%) of 77 infants were identified to have posterior fossa hemorrhage. In only two of seven infants, the lesions were seen on routine AF views. The PF approach did not increase the detection rate of posterior fossa hemorrhage. MR images confirmed cranial US findings in all cases. MR images showed punctate hemorrhage in the cerebellum in six infants with normal cranial US findings. Among the 59 infants examined with both cranial US and MR imaging, cerebellar injury was diagnosed in 11 (19%)., Conclusion: Cerebellar injury is a frequent finding in very preterm infants. Cranial US through the MF can demonstrate injury missed by using the routine AF approach. Punctate hemorrhagic lesions may remain undetected even when the MF approach is used; the prognostic implications of these smaller lesions need further attention., ((c) RSNA, 2009.)

Background: Bilateral symmetrical echogenic and echolucent areas in the white matter are frequently seen on the cranial ultrasound scans of apparently well preterm infants without overt pathology., Aim: To determine whether these features reflect maturational processes as seen on MRI., Methods: Preterm and term-born infants without overt pathology on contemporaneous brain ultrasound and MRI were studied. Ultrasound scans were compared with T(2)-weighted MRI to identify MR correlates for the bilateral and symmetrical echogenic and echolucent phenomena in the white matter seen on ultrasound., Results: Forty-four sets of scans (26 preterm, 8 term-born infants) were assessed. Echogenic features were better and more frequently seen on early ultrasound as compared to nearer term age. Echogenic blushes in the white matter correlated well with high signal intensity areas and echogenic lines with low signal intensity lines on MRI. Echolucent areas correlated with the site of the internal capsule and the myelinated posterior pons. The subplate was not reliably identified., Conclusion: Many echogenic and echolucent features in the white matter of well preterm and some term-born infants correlated well with areas of differing signal intensity on MRI. They most likely reflect normal maturational processes but the echogenic hemispheric features may represent delayed or abnormal maturation.

Magnetic Resonance Imaging is becoming more widely available and increasingly important for imaging the neonatal brain. In newborn infants it poses challenges regarding patient preparation, safety, optimal timing, and sequence optimization. These issues are addressed in this paper and indications for performing neonatal Magnetic Resonance Imaging are presented.

This study describes the incidence and evolution of brain imaging findings in very preterm infants (GA<32 weeks), assessed with sequential cranial ultrasound (cUS) throughout the neonatal period and MRI around term age. The accuracy of both tools is compared for findings obtained around term. Periventricular echodensities and intraventricular haemorrhage were the most frequent cUS findings during admission. Frequent findings on both cUS and MRI around term included ventricular dilatation, widened extracerebral spaces, and decreased cortical complexity. MRI additionally showed punctate white matter lesions and diffuse and excessive high signal intensity, but did not depict lenticulostriate vasculopathy and calcifications, and was less reliable for germinolytic and plexus cysts. cUS detected most abnormalities that have been associated with abnormal neurodevelopmental outcome.

This study describes the relation between frequent and clinically relevant brain imaging findings in very preterm infants (GA<32 weeks), assessed with sequential cranial ultrasonography throughout the neonatal period and MRI around term age, and several potential perinatal risk factors. For ultrasound findings during admission the following independent risk factors were identified: male gender for periventricular echodensities and intraventricular haemorrhage, postnatal corticosteroid treatment for cystic white matter lesions, and lower gestational age for post-haemorrhagic ventricular dilatation. For MRI findings around term age, including punctate white matter lesions, ventricular dilatation, decreased cortical complexity, and diffuse and excessive high signal intensity, no independent risk factors were found. In very preterm infants, the risk factors for frequently found changes on cranial ultrasound have largely remained unchanged over the last decades, while no risk factors could be identified for subtle and diffuse white matter injury as seen on MRI around term age.

Background and Purpose: Diffusion-weighted imaging (DWI) permits early detection and quantification of hypoxic-ischemic (HI) brain lesions. Our aim was to assess the predictive value of DWI and apparent diffusion coefficient (ADC) measurements for outcome in children with perinatal asphyxia., Materials and Methods: Term neonates underwent MR imaging within 10 days after birth because of asphyxia. MR imaging examinations were retrospectively evaluated for HI brain damage. ADC was measured in 30 standardized brain regions and in visibly abnormal areas on DWI. In survivors, developmental outcome until early school age was graded into the following categories: 1) normal, 2) mildly abnormal, and 3) definitely abnormal. For analysis, category 3 and death (category 4) were labeled "adverse," 1 and 2 were "favorable," and 2-3 and death were "abnormal" outcome. Differences in outcome between infants with and without DWI abnormalities were analyzed by using chi(2) tests. The nonparametric Mann-Whitney U test analyzed whether ADC values in visible DWI abnormalities correlated with age at imaging. Logistic regression analysis tested the predictive value for outcome of the ADC in each standardized brain region. Receiver operating characteristic analysis was used to find optimal ADC cutoff values for each region for the various outcome scores., Results: Twenty-four infants (13 male) were included. Mean age at MR imaging was 4.3 days (range, 1-9 days). Seven infants died. There was no difference in outcome between infants with and without visible DWI abnormalities. Only ADC of the posterior limb of the internal capsule correlated with age. ADC in visibly abnormal DWI regions did not have a predictive value for outcome. Of all measurements performed, only the ADC in the normal-appearing basal ganglia and brain stem correlated significantly with outcome; low ADC values were associated with abnormal/adverse outcome, and higher ADC values, with normal/favorable outcome (basal ganglia: P = .03 for abnormal, P = .01 for adverse outcome; brain stem: P = .006 for abnormal, P = .03 for adverse outcome)., Conclusions: ADC values in normal-appearing basal ganglia and brain stem correlated with outcome, independently of all MR imaging findings including those of DWI. ADC values in visibly abnormal brain tissue on DWI did not show a predictive value for outcome.

Cranial ultrasonography (CUS) is an excellent and non invasive tool for brain imaging during the neonatal period. It is traditionally performed through the anterior fontanel. Although the advantages of CUS are numerous, there are also diagnostic limitations. Alternative imaging techniques including the use of different transducer types and frequencies and of additional acoustic windows can improve image quality and the diagnostic accuracy of CUS. This review will focus on techniques to be applied for optimizing the performance of CUS in the newborn infant.

Background and Purpose: It has previously been demonstrated that comparison of signal intensity (SI) between selected brain structures on T1-weighted images enables distinction between the absence or presence of hypoxic-ischemic (HI) brain injury in young infants. The aim of the present study was to assess whether this method of brain structure T1-weighted SI comparison also enables prediction of outcome., Materials and Methods: Survivors of a group of 57 children with neonatal HI encephalopathy (HIE) grade 2 or 3 according to Sarnat and Sarnat and controls who underwent neonatal MR imaging were retrospectively assigned to 1 of 3 outcome groups at 5 years of age, depending on developmental outcome: 1) normal, 2) mildly abnormal, and 3) definitely abnormal. Gestational age was not significantly different between the HIE group (range, 35 + 5-42 + 5 weeks; mean, 39 + 4 weeks) and control group (range, 35 + 0-42 + 1 weeks; mean, 39 + 2 weeks). We calculated the predictive values of the neonatal clinical HIE classification according to Sarnat and Sarnat for outcome (neonatal death and developmental outcome in survivors). We assessed which brain structure T1-weighted SI comparison scored best for outcome prediction. Predictive values of that comparison for outcome were calculated for the entire group and for the HIE grade 2 group only, a patient group with highly variable outcome., Results: Of the 57 children, 6 died. Outcome group 1 consisted of 31; group 2, of 14; and group 3, of 6 children. The positive predictive value of the neonatal clinical classification for adverse outcome (outcome group 3 and death) was 52%; and negative predictive value, 100%. These were respectively 45% and 0% in children with HIE grade 2. Of all brain structure T1-weighted SI comparisons, that of the posterior limb of the internal capsule versus the posterolateral putamen scored best for outcome prediction. The positive predictive value for adverse outcome was 69%; and negative predictive value, 98%. In children with HIE grade 2, the positive predictive value and negative predictive value for adverse outcome were 67% and 88%., Conclusions: Brain structure T1-weighted SI comparisons are helpful to predict outcome in (near) term neonates with HIE. This finding adds to the current knowledge and clinical practice. If the SI in the posterolateral putamen is less than the SI in the posterior limb of the internal capsule, favorable outcome is very likely, whereas if the SI in the posterolateral putamen is equal to or greater than the SI in the posterior limb of the internal capsule, adverse outcome is very likely. In neonates with HIE grade 2 according to Sarnat and Sarnat, prediction of outcome is substantially improved by using these brain structure T1-weighted SI comparisons.

Introduction: Periventricular white matter (WM) echodensities, frequently seen in preterm infants, can be associated with suboptimal neurodevelopment. Major WM injury is well detected on cranial ultrasound (cUS). cUS seems less sensitive for diffuse or more subtle WM injury. Our aim was to assess the value of cUS and magnetic resonance imaging (MRI) for evaluating WM changes and the predictive value of cUS and/or MRI findings for neurodevelopmental outcome in very preterm infants with normal to severely abnormal WM on sequential high-quality cUS., Materials and Methods: Very preterm infants (<32 weeks) who had sequential cUS and one MRI within the first three postnatal months were included. Periventricular WM on cUS and MRI was compared and correlated with neurodevelopmental outcome at 2 years corrected age., Results: Forty preterm infants were studied; outcome data were available in 32. WM changes on sequential cUS were predictive of WM changes on MRI. Severely abnormal WM on cUS/MRI was predictive of adverse outcome, and normal-mildly abnormal WM of favorable outcome. Moderately abnormal WM on cUS/MRI was associated with variable outcome. Additional MRI slightly increased the predictive value of cUS in severe WM changes., Conclusion: Sequential cUS in preterm infants is reliable for detecting WM changes and predicting favorable and severely abnormal outcome. Conventional and diffusion-weighted MRI sequences before term equivalent age in very preterm infants, suggested on cUS to have mild to moderately abnormal WM, do not seem to be warranted.

Purpose: To retrospectively compare different magnetic resonance (MR) imaging techniques and pulse sequences for the depiction of brain injury in neonatal hypoxic-ischemic encephalopathy., Materials and Methods: The institutional review board approved this retrospective study and waived informed consent. Term-born neonates underwent MR imaging within 10 days after birth because of perinatal asphyxia. Two investigators separately and retrospectively evaluated T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), diffusion-weighted, and T1-weighted contrast material-enhanced MR images for presence of hypoxic-ischemic injury patterns. Interobserver agreement between the raters for visualizing abnormalities on images obtained with the individual pulse sequences was analyzed. Individual assessments were compared with the consensus reading (reference standard) to determine which techniques were best for visualizing hypoxic-ischemic damage. Last, which combination of pulse sequences had the best performance for visualizing certain injury patterns was evaluated. All analyses were repeated for infants imaged within 4 days after birth and those imaged between 4 and 10 days after birth., Results: Forty term-born neonates (22 boys; gestational age, 37 weeks to 42 weeks 2 days) were included. Interobserver agreement was moderate for all pulse sequences (intraclass correlation coefficient [ICC], 0.52-0.73). As compared with the reference standard, T1-weighted imaging performed best in both groups (infants imaged < or = 4 days and those imaged > 4 days after birth) for lesions in the basal ganglia, thalamus, and posterior limb of the internal capsule (ICC, 0.93), as well as for punctate white matter lesions (ICC, 0.88). For infarction, diffusion-weighted images were scored best in both groups (ICC, 0.86). For nonpunctate white matter lesions, T2-weighted images were scored as good in both groups (ICC, 0.59). Adding FLAIR and contrast-enhanced imaging to the combination of T1- and T2-weighted imaging and diffusion-weighted imaging did not contribute to detection of hypoxic-ischemic brain damage., Conclusion: The combination of T1- and T2-weighted MR imaging and diffusion-weighted imaging is best for detecting hypoxic-ischemic brain lesions in the early neonatal period in term-born infants.

Objective: The objective of the study was to study whether peri- and intraventricular echodensities in the brain of fetuses at risk for preterm birth are associated with changes in fetal heart rate (FHR) parameters., Study Design: Twenty preterm fetuses with peri- and intraventricular echodensities detected by transvaginal ultrasonography were matched with 20 fetuses without echodensities for gestational age, growth parameters, clinical disease, and maternal medication. Baseline FHR, long- and short-term variability, and the presence of accelerations and decelerations were analyzed with a computerized system and compared with the Wilcoxon matched-pairs signed-rank test. Both cases and controls were compared with a normal population., Results: No statistical differences in FHR parameters were found between cases with and controls without peri- and intraventricular echodensities. Both cases and controls had lower long- and short-term variabilities than the normal population., Conclusion: No association between the presence of peri- and intraventricular echodensities and specific FHR changes was demonstrated.

The differentiation between terminal zones and pathological signal intensity changes on MRI of children and young adults is of diagnostic importance. We assessed the diagnostic value of several morphological features on MRI to differentiate between terminal zones and hypoxic-ischemic white matter injury. We selected all brain MRI examinations performed in subjects up to 20 years of age showing increased signal intensity on T2-weighted images in the peritrigonal areas. 75 individuals were assigned to a patient group (n=28) if there was evidence of hypoxia-ischemia during the perinatal period or a control group (n=47). Aspect, location, extent, shape, and borders of signal intensity changes in the peritrigonal areas were studied. Signal intensity of the peritrigonal areas was related to signal intensity of surrounding white matter. Presence of Virchow Robin spaces, hypoxic-ischemic abnormalities, and local atrophy were also recorded. Chi-squared tests assessed whether presence or absence of morphological characteristics differed between patients and controls. Logistic regression analysis studied which characteristics were best to discriminate between the two groups. Very high signal intensity of the peritrigonal areas on FLAIR (Odds Ratio 25) and presence of local atrophy (Odds Ratio 14.3) were best predictors to discriminate between the two groups.

Background and Purpose: Hypoxic-ischemic cerebral changes can be difficult to distinguish from normal myelination on T1-weighted images. We hypothesized that comparing signal intensity (SI) of brain structures on T1-weighted images enables differentiation of myelination from hypoxic-ischemic brain damage., Materials and Methods: T1-weighted images, obtained in 57 infants aged 1-104 days and born after a gestational age of 35 weeks or older, were retrospectively evaluated. Subjects were assigned to a patient (n = 23, with perinatal hypoxic-ischemic encephalopathy [HIE] stage 2/3) or a control group (n = 34). In each subject, an SI score was assigned to 19 brain structures on the basis of pairwise comparisons with the other 18 structures. In both groups, mean total SI scores were calculated for the 19 structures. Independent samples t tests assessed whether the mean total score of a structure differed significantly between the 2 groups. Logistic regression assessed which comparison was best to distinguish between the groups and to predict the presence of hypoxic-ischemic injury., Results: In patients, mean total SI scores for posterolateral putamen (PP) and peri-Rolandic cortex (PC) were significantly higher (P = .000 for both). Mean total SI scores of the posterior limb of internal capsule (PLIC) and the corona radiata (CR) were significantly lower in patients (P = .000 and 0.005, respectively). Two comparisons (PLIC versus CR, PP versus PC) were best to distinguish patients and controls and to predict absence or presence of HIE (P < .0001)., Conclusion: SI changes due to hypoxia-ischemia can be differentiated from normal myelination by comparing SI of 4 brain structures on T1-weighted images.

Unlabelled: Parvovirus B19 infection in gestation has been associated with severe fetal complications such as anaemia, hydrops and fetal demise. Fetal infection in the first trimester poses the greatest risk for these complications, but infection during the third trimester is more common than previously appreciated and can be associated with severe complications, i.e. fetal death, in the absence of hydrops or classical clinical symptoms. Parvovirus B19 infection has been associated with vasculitis and pathological changes in the central nervous system, which may cause stroke. We report a newborn infant with a rare combination of a recent central nervous system infection with parvovirus B19 and a factor V Leiden mutation, who developed fetal stroke., Conclusion: Factor V Leiden mutation leads to activated protein C resistance and increases the risk of thromboembolism. Thromboembolism occurs rarely in newborns with activated protein C resistance, but can be precipitated by dehydration, asphyxia and infection. Although parvovirus B19 infection of the central nervous system may be a precipitant in neonatal and/or fetal stroke, it can also cause stroke independent of a thrombophilic mutation. In this case, both causative factors may have coincided.

Objective: The objective of the study was to determine the incidence, origin, and character of cerebral lesions in monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery., Study Design: This was a prospective study of monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery and monochorionic twins without twin-to-twin transfusion syndrome delivered at our center between June 2002 and September 2005, using cranial ultrasonography., Results: Incidence of antenatally acquired severe cerebral lesions in the twin-to-twin transfusion syndrome group was 10% (8/84) and 2% (2/108) in the non-twin-to-twin transfusion syndrome group (P = .02). Incidence of severe cerebral lesions at discharge was 14% (12/84) in the twin-to-twin transfusion syndrome group and 6% (6/108) in the non-twin-to-twin transfusion syndrome group (P = .04). Antenatal injury was responsible for severe cerebral lesions in 67% (8/12) of the twin-to-twin transfusion syndrome group., Conclusion: Incidence of severe cerebral lesions in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery is high and results mainly from antenatal injury.

Background: Advances in diagnostic testing and surgical techniques have resulted in reduced mortality in neonates with congenital heart disease (CHD) and a major concern for neurological morbidity in the presence of preoperative neurological injury., Objectives: To determine the incidence and nature of preoperative cerebral ultrasound abnormalities in neonates with major CHD and to examine the relationship between cerebral abnormalities and the type of CHD., Methods: Retrospective study; inclusion criteria: (1) neonates with major CHD admitted to the NICU over a 3-y period, (2) gestational age >35 wk, (3) documented preoperative cranial ultrasound available; exclusion criteria: (1) small for gestational age, (2) other congenital anomalies and/or chromosomal abnormalities, (3) a 5-min Apgar score <7, (4) congenital infection. Cranial ultrasounds (CUS) were reviewed without knowledge of the cardiac defect. CHDs were categorized., Results: Fifty of 108 neonates with CHD met the inclusion criteria. Twenty-one patients (42%) had abnormalities on CUS. Thirteen of these (26%) had widened ventricular and/or subarachnoid spaces, three (6%) lenticulostriate vasculopathy, one (2%) calcification in the basal nuclei, and four (8%) had acute ischaemic changes. Cerebral abnormalities occurred more frequently in patients with coarctation or hypoplastic left heart syndrome (HLHS) than transposition of the great arteries (TGA) (63% vs 14%; n.s.)., Conclusion: There is a high incidence of preoperative cerebral ultrasound abnormalities in this group of neonates with major CHD.

Cerebral ultrasound of preterm infants may show diffuse, bilateral, hyperechogenic "haze" over the thalami and basal ganglia (hyperechogenicity BGT). We explored whether this could be a pathological phenomenon. All cerebral ultrasound examinations performed in 2001 on infants < 35 weeks of age were reviewed. This resulted in a hyperechogenicity and non-hyperechogenicity group. The character of the hyperechogenicity BGT and the presence of concomitant brain lesions were noted. Detailed clinical and follow-up data from a selected group of infants < 32 weeks were reviewed and compared between the 2 groups. The incidence of hyperechogenicity BGT was 11 % (39/359) in infants < 35 weeks and 26 % (37/143) in infants < 32 weeks. Birth weight and gestational age were significantly lower and clinical course was more complicated in the hyperechogenicity group. Concomitant brain lesions were always present. In 12/39 infants with hyperechogenicity BGT, MRI (always performed for other reasons) was available, showing signal intensity changes in thalamic region in 5 infants. The neurological outcome at term was less favorable in the hyperechogenicity group, but similar at 1 year. Thus hyperechogenicity BGT mainly occurred in very small, sick infants and was always associated with cerebral pathology. MRI did not consistently show abnormalities in the thalamic region. It was not associated with a poorer outcome at 1 year.

Aim: To study the influence of dietary-supplied long-chain polyunsaturated fatty acids on structural brain maturation in preterm infants and to investigate parameters of functional brain development, relating them to structural maturation. Other studies have suggested that dietary supplementation of long-chain polyunsaturated fatty acids in preterm infants may enhance their visual development. The influence on structural brain development has never been evaluated., Methods: In a prospective, double-blind study, 42 formula-fed premature infants were randomized to be fed either a standard preterm formula without long-chain polyunsaturated fatty acids or an identical formula supplemented with docosahexaenoic acid (0.015 g/100 ml) and arachidonic acid (0.031 g/100 ml). Infants with significant cerebral damage, retinopathy, chronic disease or feeding problems were excluded. Follow-up was focused on assessment of cerebral myelination by MRI. Psychomotor, mental and visual development was analysed and flash-visual evoked potentials were recorded., Results: It was found that progress of myelination, mental and motor development and latencies of visual evoked potentials were not positively influenced by supplementation of long-chain polyunsaturated fatty acids. At each test age, visual acuity was slightly better in the supplemented infants than in the non-supplemented infants, but the difference never reached significance level, Conclusion: Supplementation of long-chain polyunsaturated fatty acids did not have a demonstrable positive influence on structural brain maturation. Related to this finding, in this small cohort of preterm infants without significant neurological damage, sample size being restricted by strict inclusion criteria and MRI procedures, no significant positive effects were found on psychomotor, mental and visual development.

In 3 studies brain maturation in 42 preterm infants with no or minor cerebral deviations was examined with MRI. With a scoring system 5 stadia in gyral development were recognized, which corresponded to the gestational age (duration of amenorrhoea of the pregnant woman). At a gestational age between 30 and 34 weeks, myelin was present in many brain stem, diencephalic and cerebellar structures, but only in a few hemispheric structures. Little progress in myelination was noticed up to the gestational age of 46 weeks. Remnants of the germinal matrix formed a sharp contrast with the immature unmyelinated periventricular white matter and had a characteristic appearance on MR images before term age. Broad periventricular zones with subtle change of signal intensity were also physiological in this age group. Zones with more outspoken signal intensity change compared with the rest of the cerebral white matter were, however, not physiological and represent mild ischaemic change of the periventricular white matter.

Background and Purpose: In the early 1980s, diagnosing periventricular leukomalacia (PVL) in neonates by using cranial sonography was possible for the first time. Our purpose was to investigate the possibility of diagnosing PVL in the acute stage by using MR imaging. We evaluated early MR features of hypoxic-ischemic brain injury in neonates with periventricular densities (flares) on cranial sonograms to determine the added value of MR imaging over sonography alone for early diagnosis of brain damage., Methods: In a prospective study, infants who showed flares and/or cysts on sonograms underwent MR imaging during the (sub)acute stage., Results: Fifty infants were classified according to the highest sonographic grade up to the day of MR imaging: 23 infants had sonographic grade 1 (flares < 1 week), 15 had sonographic grade 2 (flares > or = 1 week), four had sonographic grade 3 (small localized cysts), and eight had sonographic grade 4 (extensive periventricular cysts); none had sonographic grade 5 (multicystic leukomalacia) on the day of MR imaging. Overall, the additional information provided by MR imaging (over sonography alone) consisted of the depiction of hemorrhagic lesions in 64% of the infants. Extent and severity of the hemorrhages varied from isolated punctate lesions to extensive hemorrhages throughout the white matter; the latter were followed by cystic degeneration at autopsy in two infants. In nine of the 12 infants with cystic PVL, MR images showed more numerous or more extensive cysts. In addition, in two infants, MR images showed cysts not present on sonograms. In 32% of the infants, MR imaging provided no additional information; in these children, all but one had flares on sonograms whereas MR images showed no abnormalities or a zone of mild periventricular signal change., Conclusion: MR imaging can depict the precise site and extent of hypoxic-ischemic brain injury at an earlier stage and allows a wider differentiation of lesions as compared with sonography alone. Hemorrhagic PVL is considered to be rare, but was present in 64% of our study population.

Objective: Evaluation of the success of delayed interval delivery in multiple pregnancies., Method: Retrospective analyses of all multiple pregnancies with the birth of one child at a gestational age of 16-31 weeks (n=80). Three groups were defined: group I, unsuccessful attempt to temporize delivery, group II, interval between the first child and the other child or children 3 hours or more, with delivery of the remaining children before 28 weeks and group III, prolongation of pregnancy beyond 28 weeks., Results: In 15 multiple pregnancies (ten sets of twins, five sets of triplets), the aim was to postpone the delivery of the second (and third) child. The mean gestational age at admittance was 25 weeks. Delay of the delivery of the second child was achieved in ten cases, five in group II and five in group III. In groups II and III, the mean interval of delivery was 12 days; the gestational age at the delivery of the remaining children in these ten patients was 27 5/7 weeks. No relation could be found between the reason for admittance and the interval in delivery between the first and the other children. The only severe maternal complication was blood loss exceeding 2 liters. In the neonatal outcome of first and second children (with a gestational age of 28 weeks or more) no striking differences were observed., Conclusion: Delayed delivery in multiple pregnancies after the birth of the first child is only successful in a minority of patients and should be considered prior to the birth of the first child.

An MRI study was performed in 34 preterm infants who were clinically and neurologically normal and whose cranial ultrasound revealed no or only mild abnormalities. The postconceptional age at MRI varied between 30.6 and 37 weeks. The purpose of the study was to evaluate the significance of periventricular changes in signal intensity on MRI, comparing MRI with ultrasound. T1-weighted and T2-weighted images were assessed for changes in signal intensity of the periventricular white matter relative to the remainder of the cerebral hemispheric white matter. Cerebral MRIs of 13 postterm infants were additionally investigated. In all preterm infants small localized areas of high signal intensity on T1-weighted images and low signal intensity on T2-weighted images were seen adjacent to the frontal horns of the lateral ventricles. They faded with increasing age and were no longer seen one month after term in the group of postterm infants. The areas were considered normal before term age and probably represent remnants of the germinal matrix. Periventricular echodensities corresponded with a zone of changed signal intensity within the periventricular white matter on MRI. MRI signal change correlated with the presence and location of echodensities; the MRI signal changes slowly faded away after the echodensities disappeared.