Eur J Pediatr DOI 10.1007/s00431-007-0629-2 ORIGINAL PAPER Influence of gestational age on the type of brain injury and neuromotor outcome in high-risk neonates Christine Van den Broeck & Eveline Himpens & Piet Vanhaesebrouck & Patrick Calders & Ann Oostra Received: 16 July 2007 /Accepted: 4 October 2007 # Springer-Verlag 2007 Abstract This study was an investigation of a possible periventricular leukomalacia, 24% intraventricular hemor- correlation between either the gestational age (GA) and rhage and 18% persistent flares. There was a significant type of brain injury or between the gestational age and type, correlation between the GA and type of brain injury (P< distribution and severity of cerebral palsy (CP). Four 0.001; Cramer’s V=0.76) and between the GA and type (P= hundred sixty-one children with a birthweight ≥1250 g 0.004; Cramer’s V=0.47) and distribution (P<0.001; and GA ≥30 weeks with a complicated neonatal period and/ Cramer’s V=0.55) of CP. There was no significant correla- or brain injury on serial cerebral ultrasound were selectively tion between the GA and severity of CP. The type of brain followed at the regional Center for Developmental Disor- injury detected by serial ultrasound during the neonatal ders. The children were divided into a preterm and term period, as well as the type and location of CP detected group. There were 40 children with cerebral palsy in the during later childhood, are all GA-dependent in at-risk preterm group and 38 children with cerebral palsy in the newborn infants with a birthweight of ≥1,250 g and term group. Various types of brain injury diagnosed by GA ≥30 weeks. echography were nosologically classified. The type, distri- bution and severity of cerebral palsy were also registered. Keywords Cerebral palsy. Gestational age . Type of brain The type of brain injury most frequently occurring in the injury . Distribution of cerebral palsy. Type of cerebral palsy term group was hypoxic-ischemic injury to the basal ganglia (39%), focal ischemia (18%), subcortical hemor- Abbreviations rhage (13%) and parasagittal cerebral injury (10%). In the CP cerebral palsy preterm group 39% of the children with cerebral palsy had GA gestational age PVL periventricular leukomalacia IVH intraventricular hemorrhage Christine Van den Broeck and Eveline Himpens equally contributed to this article. : * : C. Van den Broeck E. Himpens ( ) P. Calders Introduction Rehabilitation Sciences and Physiotherapy Ghent, University College Arteveldehogeschool-Ghent University, Campus Heymans (UZ) 1B3, De Pintelaan 185, Cerebral palsy (CP) is one of the most common causes of 9000 Ghent, Belgium motor disability in childhood. CP describes a group of dis- e-mail: [email protected] orders of movement and posture causing activity limitation A. Oostra that are attributed to non-progressive disturbances occurring Center for Developmental Disorders, in the developing fetal or infant brain. Abnormal motor Ghent, Belgium behavior is the core feature of CP [3]. Barkovich [2] has shown that the brain region most sus- P. Vanhaesebrouck Department of Neonatology, University Hospital Ghent, ceptible to hypoxic/ischemic damage changes as the infant Ghent, Belgium matures. Preterm and full-term infants may thus experience Eur J Pediatr ischemia in different regions of the brain. Vohr [23] found spastic cerebral palsy if they had at least two of the following that the prevalence of any type of cerebral palsy and the criteria: abnormal posture or movement, increased tone or degree of severity of CP differed significantly for two groups hyperreflexia. An abnormal pattern of posture and/or move- of different gestational age. Therefore, probable relation- ments with involuntary, uncontrolled, recurring, occassion- ships between either the gestational age (GA) and type of ally stereotyped movements was defined as dyskinetic brain injury or between the GA and major characteristics cerebral palsy. Two types of dyskinetic cerebral palsy were of CP (i.e., type, distribution and severity) are described discerned, i.e., dystonic and choreo-athetotic cerebral palsy. [6, 10–14, 21]. Dystonic CP is described as hypokinesia (reduced activity Registers of childhood impairments and large population- and stiff movements) and hypertonia. Hyperkinesia (in- based studies monitor trends in the rates of cerebral palsy creased activity with stormy movements) and hypotonia are according to gestational age, but focus particularly on the classified as the choreo-athetotic form of dyskinetic CP. Two prevalence of CP as an assessor of the quality of perinatal mixed forms of CP are also identified, i.e., dystonia with care [6, 9, 21]. Other studies focus on the type, distribution spasticity and athetosis with spasticity. Lastly, ataxia is a and severity of cerebral palsy of term and pretem infants [1, primary disorder of coordination. Children with ataxia show 3, 6, 7, 9, 12, 21, 26]. The aim of this study was to an abnormal pattern of posture and/or movements with loss investigate a possible relationship either between the GA of muscular coordination so that movements are performed and type of brain injury, defined by serial echography, or with abnormal force, rhythm and accuracy. between GA and characteristics of CP. Different types of distribution of CP were nosologically defined. Hemiparesis is a unilateral impairment. Limbs on one side of the body are involved. Diparesis, triparesis and Patients and methods quadriparesis are bilateral motor involvements. When only the lower limbs are affected, CP is classified as diparetic. During an 8-year period (January 1995 to December 2002), When four limbs are affected CP is classified as a quadri- 461 children with a birthweight ≥1,250 g and a GA ≥30 paresis. Triparesis is used when one arm is not or only who had completed weeks with a complicated neonatal period minimally affected in a quadriparetic child [25]. and/or brain injury consulted the regional Center for Devel- The degree of severity of CP was classified as mild, opmental Disorders. The children were assessed at the moderate and severe. A child with a mild cerebral palsy corrected age of 4, 7, 12, 18 and 24 months. In the Department performs gross motor skills independently, but speed, bal- of Neonatology of the University Hospital of Ghent, an ance and coordination are reduced. CP was defined as echography was performed on day 1, 3, 7, 14 and 90 (or at the moderate if the child reached a form of independent walking time of discharge). For children with GA ≥35 weeks major with or without walking aids. When the child had no basic ultrasound findings were usually confirmed by MRI. antigravity postural control and/or could not walk, CP was The children were divided into two groups: a preterm group classified as severe. Nowadays it is common practice to use (276 children) with a gestational age (GA) between 30 and the GMFCS for the degree of severity of CP. Bax et al. [4] 37 weeks and a term group (185 children) with GA ≥37 weeks. describe a strong correspondence (K=0.583; P<0.001) be- Each child was subjected to a detailed physical and neu- tween the classification of mild-moderate-severe and the rological examination. Children were classified conforming GMFCS. to the definition proposed by the Surveillance of Cerebral Different types of brain injury detected by cerebral Palsy in Europe [3, 20]. Children were classified as having echography were identified. Fig. 1 Relative frequency of term preterm type of brain injury in the term and preterm group (PVL= 40 periventricular leukomalacia; 35 IVH=intraventricular hemor- rhage; bas=injury to basal gan- 30 glia; para=parasagittal cerebral 25 injury; focal=focal ischemia; haemor=subcortical 20 hemorrhage) 15 10 relative frequency (%) 5 0 PVL flares IVH bas para focal haemor Eur J Pediatr Fig. 2 Relative frequency of term preterm type of cerebral palsy in the term and preterm group (spast= 80 spastic; dyst=dystonic; ath=choreo-athetosis; dyst+ spast=dystonia with spasticity; 60 ath+spast=athetosis with spasticity) 40 20 relative frequency (%) 0 spast dyst ath dyst + spast ath + spast ataxia Periventricular leukomalacia (PVL) is defined as peri- For the children with CP a highly significant (P<0.001) ventricular areas of increased echogenicity evolving into correlation between the GA and the type of brain injury was small or extensive periventricular cystic lesions involving found (Cramer’s V=0.76). The most common brain injury occipital and fronto-parietal white matter. Flares are defined in the term group with CP was an injury to the basal ganglia as diffuse periventricular echodensities persistent beyond (39%), followed by focal ischemia (18%), subcortical hem- 7 days of age. Deep grey matter injury involves the thal- orrhage (13%) and parasagittal injury (10%). The diagnosis amus and basal ganglia. Parasagittal cerebral injury refers to for all four children with parasagittal injury was confirmed a lesion of the cerebral cortex and subcortical white matter by MRI. In the preterm group 39% had periventricular with a characteristic distribution. Although the injury is usually leukomalacia, 24% had an intraventricular hemorrhage and symmetrical, it may be more striking in one hemisphere as 18% of these prematurely born children had persistent flares well. Focal ischemia refers to necrosis in the territory of one or on neonatal ultrasound scans. For two preterm infants we more large cerebral blood vessels. Hemorrhage can be sub- had no neonatal ultrasound scan (Fig. 1). cortical or intraventricular. Intraventricular hemorrhage (IVH) A significant correlation (P<0.01; Cramer’s V=0.47) is a hemorrhage into the germinal matrix and the ventricles. was also found between the GA and type of CP. In the term The subcortical hemorrhages are situated in the vascular group 31% of the children had a spastic type of CP, 29% boundery (watershed) zones. For term infants these are the had dystonia, and 24% had the mixed form of dystonia with regions between the anterior and middle cerebral arteries and spasticity.