Ingrid C. van Haastert

Decreasing Incidence and Severity of Cerebral Palsy in Prematurely Born Children

OBJECTIVE To examine incidence and severity of cerebral palsy (CP), and associated factors among preterm survivors (gestational age <34 weeks), admitted to a neonatal intensive care unit from 1990-2005. STUDY DESIGN Eighteen antenatal, perinatal and postnatal factors were analyzed. The cohort was divided in four birth periods: 1990-1993 (n=661), 1994-1997 (n=726), 1998-2001 (n=723), and 2002-2005 (n=850). The Gross Motor Function Classification System was used as primary outcome measure (mean age: 32.9 ± 5.3 months). Logistic regression analyses were used. RESULTS CP incidence decreased from 6.5% in period I, to 2.6%, 2.9% and 2.2% (P<.001) in period II-IV, respectively. Simultaneously, cystic periventricular leukomalacia (c-PVL) decreased from 3.3% in period I to 1.3% in period IV (P=.004). Within the total cohort (n=3287), c-PVL grade III decreased from 2.3% in period I to 0.2% in period IV (P=.003). The number of children with Gross Motor Function Classification System levels III-V decreased from period I to IV (P=.035). Independent risk factors for CP were c-PVL and severe intraventricular hemorrhage, whereas antenatal antibiotics, presence of an arterial line, Caesarean section, and gestational age were independent protective factors. CONCLUSION CP incidence and severity decreased from 1990-1993 onward, which could be attributed to a reduction of 93% in severe c-PVL.

Myth: Cerebral palsy cannot be predicted by neonatal brain imaging

There is controversy in the literature about the value of brain imaging in neonates regarding the prediction of cerebral palsy (CP). The aim of this review was to unravel the myth that CP cannot be predicted by neuroimaging in neonates. Major intracranial lesions in the preterm infant should be recognized with sequential cranial ultrasound and will predict those with non-ambulatory CP. Magnetic resonance imaging (MRI) at term-equivalent age will refine the prediction by assessment of myelination of the posterior limb of the internal capsule. Prediction of motor outcome in preterm infants with subtle white matter injury remains difficult, even with conventional MRI. MRI is a better tool to predict outcome in the term infant with hypoxic-ischaemic encephalopathy or neonatal stroke. The use of diffusion-weighted imaging as an additional sequence adds to the predictive value for motor outcome. Sequential and dedicated neuroimaging should enable us to predict motor outcome in high risk newborns infants.

Cerebellar Volume and Proton Magnetic Resonance Spectroscopy at Term, and Neurodevelopment at 2 Years of Age in Preterm Infants.

Aim To assess the relation between cerebellar volume and spectroscopy at term equivalent age, and neurodevelopment at 24 months corrected age in preterm infants.

Neurological examination of preterm infants at term equivalent age

BACKGROUND We previously reported the neurological findings of the Dubowitz neonatal examination in a cohort of 157 low-risk preterms born between 25 and 33 weeks gestational age (GA) and examined at term equivalent age (TEA). Median and range of scores were wider than those found in term-born infants and preterms showed a different neurological behaviour in specific items. However, the cohort number was too small to draw any definitive conclusion about the distribution of findings. AIMS We provide normative data from a low-risk cohort of 380 preterm infants; we also assess the findings and their relationship to motor outcome in preterms with major cranial ultrasound (US) abnormality. STUDY DESIGN We assessed, at TEA, 380 low-risk preterms born <35 weeks gestation (range 25-34.9, median 29) with normal 2 year motor outcome and 85 preterm infants with major US abnormality. RESULTS At TEA low-risk preterms had less flexor limb tone, poorer head control but better visual following than term-born infants. For 28/34 of the neurological items the range and median scores were similar across gestational ages. In infants with major US lesions the range and median scores differed from low-risk preterms in 20/34 items; 40% of infants developing a diplegia and 80% developing a tetraplegia had >7 items outside the 90th centile; all infants with >12 items outside the 90th centile developed a tetraplegia. CONCLUSIONS We provide reference values for the neurological examination of low-risk preterms at TEA. In infants with major US abnormality the number of items outside the 90th centile was an indicator of outcome severity.

Does Diffusion Tensor Imaging-Based Tractography at 3 Months of Age Contribute to the Prediction of Motor Outcome After Perinatal Arterial Ischemic Stroke?

Background and Purpose— After perinatal arterial ischemic stroke, diffusion-weighted imaging (DWI) and early evaluation of spontaneous motor behavior can be used to predict the development of unilateral motor deficits. The aim of this study was to investigate whether diffusion tensor imaging-based tractography at 3 months of age contributes to this prediction. Methods— Twenty-two infants with unilateral perinatal arterial ischemic stroke were included and scanned during the neonatal period. DWI was used to assess restricted diffusion in the cerebral peduncle. At the age of 3 months, diffusion tensor imaging-based tractography of the corticospinal tracts was performed along with assessment of the movement repertoire. The role of DWI, diffusion tensor imaging, and motor assessment in predicting unilateral motor deficits were compared by calculating the positive and negative predictive values for each assessment. Results— Eleven infants (50%) showed abnormal motor behavior at 3 months with subsequent development of unilateral motor deficits in 8 as determined at follow-up (9–48 months, positive predictive value 73%). Diffusion tensor imaging-based tractography correctly predicted the development of unilateral motor deficits in all 8 infants (positive predictive value 100%). A diagnostic neonatal DWI was available in 20 of 22 (91%) infants. Seven infants showed an abnormal DWI, resulting in unilateral motor deficits in 6 infants (positive predictive value 86%). All assessments had a negative predictive value of 100%. Conclusions— Diffusion tensor imaging-based tractography at 3 months can be used to predict neurodevelopmental outcome after perinatal arterial ischemic stroke. It has a similar predictive value as DWI in the neonatal period and can especially be of additional value in case of an indecisive neonatal DWI or unexpected abnormal early motor development.

Neurological Injury After Neonatal Cardiac Surgery A Randomized, Controlled Trial of 2 Perfusion Techniques

Background— Complex neonatal cardiac surgery is associated with cerebral injury. In particular, aortic arch repair, requiring either deep hypothermic circulatory arrest (DHCA) or antegrade cerebral perfusion (ACP), entails a high risk of perioperative injury. It is unknown whether ACP results in less cerebral injury than DHCA. Methods and Results— Thirty-seven neonates with an aortic arch obstruction presenting for univentricular or biventricular repair were randomized to either DHCA or ACP. Preoperatively and 1 week after surgery, magnetic resonance imaging was performed in 36 patients (1 patient died during the hospital stay). The presence of new postoperative cerebral injury was scored, and results were entered into a sequential analysis, which allows for immediate data analysis. After the 36th patient, it was clear that there was no difference between DHCA and ACP in terms of new cerebral injury. Preoperatively, 50% of patients had evidence of cerebral injury. Postoperatively, 14 of 18 DHCA patients (78%) had new injury versus 13 of 18 ACP patients (72%) (P=0.66). White matter injury was the most common type of injury in both groups, but central infarctions occurred exclusively after ACP (0 vs 6/18 [33%]; P=0.02). Early motor and cognitive outcomes at 24 months were assessed and were similar between groups (P=0.28 and P=0.25, respectively). Additional analysis revealed lower postoperative arterial PCO2 as a risk factor for new white matter injury (P=0.04). Conclusions— In this group of neonates undergoing complex cardiac surgery, we were unable to demonstrate a difference in the incidence of perioperative cerebral injury after ACP compared with DHCA. Both techniques resulted in a high incidence of new white matter injury, with central infarctions occurring exclusively after ACP. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01032876.Background— Complex neonatal cardiac surgery is associated with cerebral injury. In particular, aortic arch repair, requiring either deep hypothermic circulatory arrest (DHCA) or antegrade cerebral perfusion (ACP), entails a high risk of perioperative injury. It is unknown whether ACP results in less cerebral injury than DHCA. Methods and Results— Thirty-seven neonates with an aortic arch obstruction presenting for univentricular or biventricular repair were randomized to either DHCA or ACP. Preoperatively and 1 week after surgery, magnetic resonance imaging was performed in 36 patients (1 patient died during the hospital stay). The presence of new postoperative cerebral injury was scored, and results were entered into a sequential analysis, which allows for immediate data analysis. After the 36th patient, it was clear that there was no difference between DHCA and ACP in terms of new cerebral injury. Preoperatively, 50% of patients had evidence of cerebral injury. Postoperatively, 14 of 18 DHCA patients (78%) had new injury versus 13 of 18 ACP patients (72%) ( P =0.66). White matter injury was the most common type of injury in both groups, but central infarctions occurred exclusively after ACP (0 vs 6/18 [33%]; P =0.02). Early motor and cognitive outcomes at 24 months were assessed and were similar between groups ( P =0.28 and P =0.25, respectively). Additional analysis revealed lower postoperative arterial Pco2 as a risk factor for new white matter injury ( P =0.04). Conclusions— In this group of neonates undergoing complex cardiac surgery, we were unable to demonstrate a difference in the incidence of perioperative cerebral injury after ACP compared with DHCA. Both techniques resulted in a high incidence of new white matter injury, with central infarctions occurring exclusively after ACP. Clinical Trial Registration— URL: . Unique identifier: [NCT01032876][1]. # CLINICAL PERSPECTIVE {#article-title-31} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01032876&atom=%2Fcirculationaha%2F129%2F2%2F224.atom

Fiber Tracking at Term Displays Gender Differences Regarding Cognitive and Motor Outcome at 2 Years of Age in Preterm Infants

White matter microstructural changes can be detected with diffusion tensor imaging. It was hypothesized that diffusion parameters in the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) bundles in preterm infants at term equivalent age (TEA) were associated with neurodevelopment at 2 y corrected age. In 67 preterm infants, fiber tracking was performed at TEA for the CC and both PLIC bundles. Volume, length, fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity were determined for the three bundles. These parameters were assessed in relation to outcome on the Bayley Scales of Infant and Toddler Development III. In girls, volume and length of the CC bundle and right PLIC bundle volume were associated with cognition. In boys, volume, FA, mean and radial diffusivity, and length of the left PLIC were associated with fine motor scores. Correction for GA, birth weight, intraventricular hemorrhage, white matter injury, and maternal education did not change the results. Fiber tracking parameters in the PLIC and CC bundles in preterm infants at TEA revealed different associations with neurodevelopment between boys and girls. This study suggested that fiber tracking is a useful method to predict neurodevelopment in preterm infants.

Different Patterns of Punctate White Matter Lesions in Serially Scanned Preterm Infants

Background and Purpose With the increased use of MRI in preterm infants, punctate white matter lesions (PWML) are more often recognized. The aim of this study was to describe the incidence and characteristics of these lesions as well as short-term outcome in a cohort of serially scanned preterm infants, using both conventional imaging, diffusion (DWI) and susceptibility (SWI) weighted imaging. Materials and Methods 112 preterm infants with 2 MRIs in the neonatal period, with evidence of punctate white matter lesions, were included. Appearance, lesion load, location, and abnormalities on DWI and SWI were scored and outcome data were collected. Results Different patterns of punctate white matter lesions did appear: a linear appearance associated with signal loss on SWI, and a cluster appearance associated with restricted diffusion on DWI on the first MRI. Cluster and mixed lesions on the first scan changed in appearance in over 50% on the second scan, whereas linear lesions generally kept their appearance. Lesions were only visible on the early scan in 33%, and were only seen at term equivalent age in 20%. Nine infants developed cerebral palsy, due to additional overt white matter lesions in six. Conclusion Two patterns of punctate white matter lesions were identified: one with loss of signal on SWI in a linear appearance, and the other with DWI lesions with restricted diffusion in a cluster appearance. These different patterns are suggestive of a difference in underlying pathophysiology. To reliably classify PWML in the preterm infant in either pattern, an early MRI with DWI and SWI sequences is required.

Diffusion-weighted imaging changes in cerebral watershed distribution following neonatal encephalopathy are not invariably associated with an adverse outcome.

Patterns of injury in term‐born infants with neonatal encephalopathy following hypoxia–ischaemia are seen earlier and are more conspicuous on diffusion‐weighted magnetic resonance imaging (DW‐MRI) than on conventional imaging. Although the prognostic value of DW‐MRI in infants with basal ganglia and thalamic damage has been established, data in infants in whom there is extensive injury in a watershed distribution are limited. The aim of this study was to assess cognitive and functional motor outcome in a cohort of infants with changes in a predominantly watershed distribution injury on neonatal cerebral MRI, including DWI.

Atypical timing and presentation of periventricular haemorrhagic infarction in preterm infants: the role of thrombophilia

Aim  Periventricular haemorrhagic infarction (PVHI) is a complication of preterm birth associated with cardiorespiratory instability. To date, the role of thrombophilia as a possible additional risk factor in infants with atypical timing and presentation of PVHI has not been investigated.