Margaretha J. Brouwer

New Reference Values for the Neonatal Cerebral Ventricles

PURPOSEnTo establish new cross-sectional reference values for the size of the lateral ventricles in a large cohort of neonates between 24 and 42 weeks gestational age (GA) as well as longitudinal reference values for the follow-up of very preterm infants born at less than 30 weeks gestation.nnnMATERIALS AND METHODSnInstitutional review board approval and parental written informed consent were obtained for this prospective cohort study of 625 neonates (58% male patients) with a median GA of 33.4 weeks (range, 24.7-42.6 weeks). All infants underwent cranial ultrasonography (US) within 4 days after birth to evaluate the size of the lateral ventricles. Scanning was repeated in 301 preterm and term neonates within the 1st week of life to assess the presence of ventricular reopening. Seventy-nine very preterm infants (GA, <30 weeks) were prospectively included for cranial US at term-equivalent age (TEA). US measurements were performed of the ventricular index (VI), anterior horn width (AHW), and thalamo-occipital distance (TOD). Statistical analysis was conducted by using a paired t test, multilevel analysis, and analysis of covariance.nnnRESULTSnCross-sectional reference values for the VI and TOD increased with maturity, whereas the AHW remained constant. Vaginal birth was independently associated with a slightly smaller AHW following birth and with an increase in AHW within the 1st week of life (P < .05). Preterm-born infants showed a larger ventricular size at TEA compared with term infants (P < .001).nnnCONCLUSIONnNew cross-sectional and longitudinal reference curves were established for the size of the neonatal lateral ventricles, which may allow for early identification and quantification of ventriculomegaly due to either posthemorrhagic ventricular dilation or periventricular white matter loss.

Ultrasound measurements of the lateral ventricles in neonates: why, how and when? A systematic review

Germinal matrix‐intraventricular haemorrhage and subsequent post‐haemorrhagic ventricular dilatation (PHVD) are frequently encountered complications in preterm neonates. As progressive dilatation of the lateral ventricles may be associated with elevated intracranial pressure, ultrasound measurements of ventricular size play a major role in the evaluation of neonates at risk of ventricular dilatation as well as in assessing the effect of intervention for PHVD. A systematic search was carried out in Medline and Embase to identify neonatal and foetal ultrasound studies on lateral ventricular size. This review presents an overview of the available data concerning neonatal reference values for lateral ventricular size, the influence of gender, ventricular asymmetry and the effect of the mode of delivery on the phenomenon of ventricular reopening following birth.

European perspective on the diagnosis and treatment of posthaemorrhagic ventricular dilatation

Background Posthaemorrhagic ventricular dilatation (PHVD) is a serious complication of prematurity with subsequent disabilities. The diagnostic and therapeutic approaches to PHVD vary among neonatal centres. Aim To gain more insight into the different diagnostic criteria and treatment policies on PHVD among neonatal intensive care units across Europe. Methods A PHVD questionnaire was designed and sent to neonatologists in 37 European centres. Results A response was obtained from 32/37 (86%) centres located in 17 European countries. An overall estimated incidence of 7% was reported for severe intraventricular haemorrhages (grades III or IV according to Papile) among premature neonates born below 30 weeks’ gestation. Approximately half of these infants developed PHVD, of whom three-quarters required intervention. Ultrasound measurements of ventricular size were most commonly used to diagnose PHVD (94%). No consensus existed on which ventricular parameters needed to be enlarged and when to start treatment of PHVD. Early intervention (ie, initiated after the ventricular index (VI) exceeded the 97th percentile (p97) according to Levene) was provided in 8/32 centres (25%), whereas 23/32 centres (72%) first started therapy once the VI had crossed the p97+4 mm line and/or when neonates presented with a progressive increase in head circumference or with clinical symptoms of raised intracranial pressure. Wide variation was seen with respect to the applied therapy modalities for cerebrospinal fluid drainage. Conclusion This survey shows that diagnostic and therapeutic approaches to neonates with PHVD vary considerably. Uniform diagnostic criteria would facilitate studies to assess optimal timing and mode of intervention.

Sequential Cranial Ultrasound and Cerebellar Diffusion Weighted Imaging Contribute to the Early Prognosis of Neurodevelopmental Outcome in Preterm Infants

Objective To evaluate the contribution of sequential cranial ultrasound (cUS) and term-equivalent age magnetic resonance imaging (TEA-MRI) including diffusion weighted imaging (DWI) to the early prognosis of neurodevelopmental outcome in a cohort of very preterm infants (gestational age [GA] <31 weeks). Study design In total, 93 preterm infants (median [range] GA in weeks: 28.3 [25.0–30.9]) were enrolled in this prospective cohort study and underwent early and term cUS as well as TEA-MRI including DWI. Early cUS abnormalities were classified as normal, mild, moderate or severe. Term cUS was evaluated for ex-vacuo ventriculomegaly (VM) and enlargement of the extracerebral cerebrospinal fluid (eCSF) space. Abnormalities on T1- and T2-weighted TEA-MRI were scored according to Kidokoro et al. Using DWI at TEA, apparent diffusion coefficients (ADCs) were measured in four white matter regions bilaterally and both cerebellar hemispheres. Neurodevelopmental outcome was assessed at two years’ corrected age (CA) using the Bayley Scales of Infant and Toddler Development, third edition. Linear regression analysis was conducted to explore the correlation between the different neuroimaging modalities and outcome. Results Moderate/severe abnormalities on early cUS, ex-vacuo VM and enlargement of the eCSF space on term cUS and increased cerebellar ADC values on term DWI were independently associated with worse motor outcome (p<.05). Ex-vacuo VM on term cUS was also related to worse cognitive performance at two years’ CA (p<.01). Conclusion These data support the clinical value of sequential cUS and recommend repeating cUS at TEA. In particular, assessment of moderate/severe early cUS abnormalities and ex-vacuo VM on term cUS provides important prognostic information. Cerebellar ADC values may further aid in the prognostication of gross motor function.

Effects of Posthemorrhagic Ventricular Dilatation in the Preterm Infant on Brain Volumes and White Matter Diffusion Variables at Term-Equivalent Age

OBJECTIVEnTo evaluate the differential impact of germinal matrix-intraventricular hemorrhage (GMH-IVH) and posthemorrhagic ventricular dilatation (PHVD) on brain and cerebrospinal fluid (CSF) volumes and diffusion variables in preterm born infants at term-equivalent age (TEA).nnnSTUDY DESIGNnNineteen infants (gestational age <31xa0weeks) with GMH-IVH grade II-III according to Papile etxa0al and subsequent PHVD requiring intervention were matched against 19 controls with GMH-IVH grade II but no PHVD and 19 controls without GMH-IVH. Outcome variables on magnetic resonance imaging (MRI) including diffusion weighted imaging at TEA were volumes of white matter, cortical gray matter, deep gray matter, brainstem, cerebellum, ventricles, extracerebral CSF, total brain tissue, and intracranial volume (ICV), as well as white matter and cerebellar apparent diffusion coefficients (ADCs). Effects of GMH-IVH and PHVD on TEA-MRI measurements were evaluated using multivariable regression analysis. Brain and CSF volumes were adjusted for ICV to account for differences in bodyweight at TEA-MRI and ICV between cases and controls.nnnRESULTSnPHVD was independently associated with volumes of deep gray matter (β [95% CI]: -1.4xa0cc [-2.3; -.5]), cerebellum (-2.7xa0cc [-3.8; -1.6]), ventricles (+12.7xa0cc [7.9; 17.4]), and extracerebral CSF (-11.2xa0cc [-19.2; -3.3]), and with ADC values in occipital, parieto-occipital, and parietal white matter (β: +.066-.119×10(-3)xa0mm(2)/s) on TEA-MRI (Pxa0<xa0.05). No associations were found between GMH-IVH grade II-III and brain and CSF volumes or ADC values at TEA.nnnCONCLUSIONSnPHVD was negatively related to deep gray matter and cerebellar volumes and positively to white matter ADC values on TEA-MRI, despite early intervention for PHVD in the majority of the infants. These relationships were not observed for GMH-IVH.

Preterm brain injury on term-equivalent age MRI in relation to perinatal factors and neurodevelopmental outcome at two years

Objectives First, to apply a recently extended scoring system for preterm brain injury at term-equivalent age (TEA-)MRI in a regional extremely preterm cohort; second, to identify independent perinatal factors associated with this score; and third, to assess the prognostic value of this TEA-MRI score with respect to early neurodevelopmental outcome. Study design 239 extremely preterm infants (median gestational age [range] in weeks: 26.6 [24.3–27.9]), admitted to the Wilhelmina Children’s Hospital between 2006 and 2012 were included. Brain abnormalities in white matter, cortical and deep grey matter and cerebellum and brain growth were scored on T1- and T2-weighted TEA-MRI using the Kidokoro scoring system. Neurodevelopmental outcome was assessed at two years corrected age using the Bayley Scales of Infant and Toddler Development, third edition. The association between TEA-MRI and perinatal factors as well as neurodevelopmental outcome was evaluated using multivariable regression analysis. Results The distribution of brain abnormalities and brain metrics in the Utrecht cohort differed from the original St. Louis cohort (p < .05). Mechanical ventilation >7 days (β [95% confidence interval, CI]: 1.3 [.5; 2.0]) and parenteral nutrition >21 days (2.2 [1.2; 3.2]) were independently associated with higher global brain abnormality scores (p < .001). Global brain abnormality scores were inversely associated with cognitive (β in composite scores [95% CI]: -.7 [-1.2; -.2], p = .004), fine motor (β in scaled scores [95% CI]: -.1 [-.3; -.0], p = .007) and gross motor outcome (β in scaled scores [95% CI]: -.2 [-.3; -.1], p < .001) at two years corrected age, although the explained variances were low (R2 ≤.219). Conclusion Patterns of brain injury differed between cohorts. Prolonged mechanical ventilation and parenteral nutrition were identified as independent perinatal risk factors. The prognostic value of the TEA-MRI score was rather limited in this well-performing cohort.

202 Post-Haemorrhagic Ventricular Dilatation and Adc Measurements in the White Matter in Preterm Born Infants at Term Equivalent Age

202 Post-Haemorrhagic Ventricular Dilatation and Adc Measurements in the White Matter in Preterm Born Infants at Term Equivalent Age

The Impact of Low-Grade Germinal Matrix-Intraventricular Hemorrhage on Neurodevelopmental Outcome of Very Preterm Infants

Background: Very preterm infants often show germinal matrix-intraventricular hemorrhage (GMH-IVH) on cranial ultrasound (cUS). Aim: To determine the impact of low-grade GMH-IVH on early neurodevelopmental outcome in very preterm infants. Methods: A retrospective case-control study in very preterm infants with and without low-grade GMH-IVH on cUS. Additional magnetic resonance imaging (MRI) was available in all infants with a gestational age (GA) <28 weeks and high-risk infants >28 weeks. Infants were seen at 2 years corrected age to assess neurodevelopment. Results: In total, 136 infants (GA 24-32 weeks) with low-grade GMH-IVH on cUS were matched with 255 controls. Outcome data was available for 342 (87%) infants. Adverse outcome (i.e., cerebral palsy [CP], neurodevelopmental delay) was present in 11 (9%) cases and 20 (9%) controls. No statistically significant differences in outcome were found between cases and controls. Additional MRI was performed in 165/391 infants (42%) and showed additional lesions in 73 (44%) infants that could explain subsequent development of CP in 2 out of 5 infants and epilepsy in 1 of 2 infants. Conclusion: Very preterm infants with low-grade GMH-IVH on cUS have a similar early neurodevelopmental outcome compared with controls. Additional MRI showed mostly subtle abnormalities that were missed with cUS, but these could not explain subsequent development of CP and developmental delay in all infants.