Multi-domain cognitive impairments at school age in very preterm-born children compared to term-born peers.

BACKGROUND: Preterm infants are at risk for functional impairments in motor, cognitive, and behavioral development that may persist into childhood. The aim of this study was to determine the co-occurrence of cognitive impairments in multiple cognitive domains at school age in very preterm born children compared to term-born children. METHODS: Comparative study including 60 very preterm-born children (gestational age ≤ 32 weeks) and 120 term-born controls. At school age, we assessed intelligence with the WISC-III, and visuomotor integration with the NEPSY-II, verbal memory with the AVLT, attention with the TEA-ch, and executive functioning with the BRIEF. We investigated co-occurrence of various abnormal (<5th percentile) and suspect-abnormal (<15th percentile, including both suspect and abnormal) cognitive functions. RESULTS: At mean age 8.8 years, 15% of preterm children had abnormal outcomes in multiple cognitive functions (≥2), versus 3% of the controls (odds ratio, OR 4.65, 95%-confidence interval, CI 1.33-16.35). For multiple suspect-abnormal cognitive outcomes, rates were 55% versus 25% (OR 3.02, 95%-CI 1.49-6.12). We found no pattern of co-occurrence of cognitive impairments among preterm children that deviated from term-born controls. However, low performance IQ was more frequently accompanied by additional cognitive impairments in preterms than in controls (OR 5.43, 95%-CI 1.75-16.81). CONCLUSIONS: A majority of preterm children showed co-occurrence of impairments in multiple cognitive domains, but with no specific pattern of impairments. The occurrence of multi-domain cognitive impairments is higher in preterms but this seems to reflect a general increase, not one with a pattern specific for preterm-born children.

Prenatal exposure to PCBs and neurological and sexual/pubertal development from birth to adolescence.

Several chemical compounds are resistant to degradation and end up in the food chain. One group of these chemicals is polychlorinated biphenyls (PCBs) which are used as flame retardants and plasticizers. Although PCBs were banned several decades ago, PCBs are still found in environmental media, including in the body of humans. PCBs are transferred from mother to fetus via the placenta during pregnancy. Considering that the prenatal period is a sensitive period during which essential developmental processes take place, exposure to environmental chemicals might have considerable and permanent consequences for outcomes in later life. The aim of this review is to provide an update on the latest insights on the effects of prenatal exposure to PCBs on neurological, sexual and pubertal development in children. We give an overview of recent literature, and discuss it in the light of the findings in a unique Dutch birth cohort, with data on both neurological and pubertal development into adolescence. The findings in the studies included in this review, together with the findings in the Dutch cohort, demonstrate that prenatal exposure to PCBs can interfere with normal child development, not only during the perinatal period, but up to and including adolescence. Higher prenatal exposure to PCBs was found to be both negatively and positively associated with neurodevelopmental outcomes. Regarding pubertal development, higher prenatal PCB exposure was found to be associated with more advanced pubertal development, also in the Dutch cohort, whereas other studies also found delayed pubertal development. These findings raise concern regarding the effects of man-made chemical compounds on child development. They further contribute to the awareness of how environmental chemical compounds can interfere with child development and negatively influence healthy ageing.

Functional outcome at school age of neonatal post-hemorrhagic ventricular dilatation.

BACKGROUND: Specific knowledge about the functional outcome of preterm born children with post-hemorrhagic ventricular dilatation (PHVD) is lacking. OBJECTIVES: To determine functional outcome at school age in children with post-hemorrhagic ventricular dilatation and to identify whether PHVD characteristics increased the risk for deficits. METHODS: Single-center case-control study. Included were preterm children born between 1996 and 2003 who had PHVD in their neonatal period. The controls were children matched for gestation, gender, and year of birth. At school age, using standardized tests and questionnaires, we assessed intelligence, attention, verbal memory, executive functioning, visual perception, visuomotor integration, motor skills, and behavior. RESULTS: Of 34 children with PHVD 28 survived, three of whom could not be tested at school age (one child's parents declined and two were lost to follow-up). At a mean age of 10years (6-14years) the total and verbal IQs of the remaining 25 children (17 boys, 8 girls) were significantly lower compared to controls (difference in total IQ-14 points, verbal IQ-9 points, P=0.001and P=0.009, respectively). After adjustment for possible confounders, the performance of the PHVD group was poorer on visual perception and attention tests. Selective attention showed a trend toward risk of borderline and abnormal scores (OR 4.03, 95%-CI 0.84-19.2). Within the PHVD group, total IQ was significantly lower (P=0.048) in those who had undergone surgical intervention (n=12). CONCLUSION: At school age, intelligence, attention, and visual perception were more affected in the PHVD group than in the matched controls. Surgical intervention was associated with lower IQ scores.

Neonatal DTI early after birth predicts motor outcome in preterm infants with periventricular hemorrhagic infarction.

BACKGROUND: To determine the association between early neonatal diffusion tensor imaging (DTI) and the development of unilateral spastic cerebral palsy (USCP) in preterm infants with periventricular hemorrhagic infarction (PVHI). METHODS: Preterm infants with PVHI were assessed with early (≤4 wk after birth) and term-equivalent age MRI-DTI. Involvement of corticospinal tracts was assessed by visual assessment of the posterior limb of the internal capsule (PLIC) on DTI (classified asymmetrical, equivocal, or symmetrical) and by an atlas-based approach calculating fractional anisotropy asymmetry index in the PLIC. Motor outcome was assessed at ≥15 mo corrected age. RESULTS: Seven out of 23 infants with PVHI developed USCP. Their PLIC was visually scored as asymmetrical in 6 and equivocal in 1 on the early DTI. Thirteen out of 16 infants with a symmetrical motor development had a symmetrical PLIC on early DTI, the remaining 3 were equivocal. All infants with USCP had a fractional anisotropy asymmetry index of >0.05 (optimal cut-off value) on early DTI. In infants with a symmetrical motor development (n = 16), 14 had an asymmetry index ≤0.05 while 2 had an index >0.05. CONCLUSION: DTI in preterm infants with PVHI within a few weeks after birth is associated with later motor development.

Development of the Corticospinal and Callosal Tracts from Extremely Premature Birth up to 2 Years of Age.

White matter tracts mature asymmetrically during development, and this development can be studied using diffusion magnetic resonance imaging. The aims of this study were i. to generate dynamic population-averaged white matter registration templates covering in detail the period from 25 weeks gestational age to term, and extending to 2 years of age based on DTI and fractional anisotropy, ii. to produce tract-specific probability maps of the corticospinal tracts, forceps major and forceps minor using probabilistic tractography, and iii. to assess the development of these tracts throughout this critical period of neurodevelopment. We found evidence for asymmetric development across the fiber bundles studied, with the corticospinal tracts showing earlier maturation (as measured by fractional anisotropy) but slower volumetric growth compared to the callosal fibers. We also found evidence for an anterior to posterior gradient in white matter microstructure development (as measured by mean diffusivity) in the callosal fibers, with the posterior forceps major developing at a faster rate than the anterior forceps minor in this age range. Finally, we report a protocol for delineating callosal and corticospinal fibers in extremely premature cohorts, and make available population-averaged registration templates and a probabilistic tract atlas which we hope will be useful for future neonatal and infant white-matter imaging studies.

Developmental neurotoxicity of persistent organic pollutants: an update on childhood outcome.

Organohalogens are persistent organic pollutants that have a wide range of chemical application. There is growing evidence that several of these chemical compounds interfere with human development in various ways. The aim of this review is to provide an update on the relationship between various persistent organic pollutants and childhood neurodevelopmental outcome from studies from the past 10 years. This review focuses on exposure to polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs) and dichlorodiphenyldichloroethylene (DDE), and in addition on exposure to phthalates, bisphenol A, and perfluorinated compounds and their associations with neurodevelopmental outcome in childhood, up to 18 years of age. This review shows that exposure to environmental chemicals affects neurodevelopmental outcome in children. Regarding exposure to PCBs and OH-PCBs, most studies report no or inverse associations with neurodevelopmental outcomes. Regarding exposure to PBDEs, lower mental development, psychomotor development and IQ were found at preschool age, and poorer attention at school age. Regarding exposure to DDE, most studies reported inverse associations with outcome, while others found no associations. Significant relations were particularly found at early infancy on psychomotor development, on attention and ADHD, whereas at school age, no adverse relationships were described. Additionally, several studies report gender-related vulnerability. Future research should focus on the long-term effects of prenatal and childhood exposure to these environmental chemicals, on sex-specific and combined exposure effects of environmental chemicals, and on possible mechanisms by which these chemicals have their effects on neurodevelopmental and behavioral outcomes.

Motor development in 3-month-old healthy term-born infants is associated with cognitive and behavioural outcomes at early school age.

AIM: To determine whether motor development at 3 months of age is associated with cognitive, motor, and behavioural outcomes in healthy children at early school age. METHOD: In this cohort study, we included 74 term-born, healthy children (44 males, 30 females; median gestational age 40.1 wks, range 38.0-42.6 wks). From video recordings (median 12.9 wks, range 9.3-18.6 wks), we assessed the quality of fidgety movements, and calculated a motor optimality score. At school age (median 5 y 11 mo, range 5 y 8 mo-7 y 6 mo), we performed detailed cognitive, motor, and behavioural assessments. We examined whether aspects of motor development were associated with functional outcomes. RESULTS: An age-adequate motor repertoire, in particular the presence of antigravity, midline leg, and manipulation movements, was related to poorer cognition, whereas variable finger postures was related to better cognition. Children with a monotonous concurrent motor repertoire had better ball skills but experienced more behavioural problems. The presence of antigravity movements tended to be associated with abnormal recognition (odds ratio [OR] 4.4, 95% confidence interval [CI], 0.9-21; R(2) =0.17; p=0.070), where the absence of variable finger postures was associated with borderline and abnormal visual-spatial perception (OR 20, 95% CI, 1.7-238; R(2) =0.39; p=0.018). INTERPRETATION: Detailed aspects of motor development at 3 months of age are associated with cognition and behaviour, but not with motor outcome, in healthy children at early school age. Our findings suggest that early motor development may be the basis for later cognitive and behavioural performance. Since the associations were only moderate, possible environmental influences should be acknowledged.

Functional outcome at school age of preterm-born children treated with high-dose dexamethasone.

BACKGROUND: Postnatal dexamethasone (DXM) treatment is associated with adverse motor outcome. It is largely unknown as to what extent functional outcome at school age is affected. AIMS: Our first aim was to determine motor, cognitive, and behavioural outcome at school age of preterm-born children treated with high-dose DXM for pulmonary problems. Our second aim was to identify DXM-related risk factors for adverse outcome. STUDY DESIGN: In this cohort study, we included 53 very preterm-born children treated with DXM (starting dose 0.5mg/kg/d) after the first week of life. At the median age of 9 years, we performed a detailed neuropsychological assessment. RESULTS: Compared to the norm population, DXM-treated children scored worse on the Movement-ABC (abnormal fine motor, ball skills and balance: 59%, 47% and 30%, respectively). They more often had total (36%), verbal (32%) and performance IQs (55%) below 85 (P<.001, P=.002, P<.001, respectively). On each of the remaining measures, DXM-treated children scored worse than the norm population, except for verbal long-term memory and verbal recognition memory. DXM-related risk factors were associated with poorer performance. CONCLUSIONS: At school age, multiple domains of functional outcome were affected in DXM-treated children. Risk factors related to the use of DXM should be considered as serious potentiaters of adverse outcome in children treated with high-dose DXM.

Development of fine motor skills in preterm infants.

Fine motor skills are related to functioning in daily life and at school. We reviewed the status of knowledge, in preterm children, on the development of fine motor skills, the relation with gross motor skills, and risk factors for impaired fine motor skills. We searched the past 15 years in PubMed, using ['motor skills' or 'fine motor function' and 'preterm infant'] as the search string. Impaired gross and fine motor skills are among the most frequently occurring problems encountered by preterm children who do not develop cerebral palsy. The prevalence is around 40% for mild to moderate impairment and 20% for moderate impairment. Fine motor skill scores on the Movement Assessment Battery for Children are about 0.62 of a standard deviation lower compared with term children. Risk factors for fine motor impairments include moderately preterm birth (odds ratio [OR] 2.0) and, among very preterm children (<32 wk gestation), intra-uterine growth restriction (ORs 2-3), inflammatory conditions (late-onset sepsis and necrotizing enterocolitis, ORs 3-5), and dexamethasone therapy for bronchopulmonary dysplasia (OR 2.7). A better understanding of factors that play a role in the development of and recovery from brain injury could guide future intervention attempts aimed at improving fine motor skills of preterm children.

Motor and cognitive outcome at school age of children with surgically treated intestinal obstructions in the neonatal period.

BACKGROUND: The motor and cognitive outcome at school age of newborn children with surgically treated intestinal obstructions is unknown. Physiological stress and anesthesia may potentially be harmful in the period of early brain development in newborn infants. OBJECTIVE: To determine motor and cognitive outcome at school age in children with surgically treated intestinal obstructions as newborns, and to identify clinical risk factors for adverse outcome. STUDY DESIGN: Cohort study of infants born between 1995 and 2002 with atresia, stenosis, or intestinal malrotation. At 6 to 13years we assessed their motor functions, intelligence, attention, visual perception, visuomotor integration, and verbal memory. RESULTS: Of 44 children three (7%) died. Twenty-seven survivors (66%) were included for follow-up (median gestational age 36.7weeks, birth weight 3000g). Motor outcome was abnormal (<5th percentile) in 22% of the children, which was significantly more than in the norm population (P<0.01). Scores on selective attention were abnormal in 15% of the children (P<0.01). Other cognitive functions were not affected. Lower birth weight and intestinal perforation were risk factors for poorer motor outcome (R(2)=53.0%), intrauterine growth restriction was a risk factor for poorer selective attention (R(2)=36.6%). CONCLUSIONS: Children treated surgically for intestinal obstructions in the neonatal period had an increased risk for poor motor functioning and selective attention at school age. Low birth weight, intrauterine growth restriction and intestinal perforation were risk factors for adverse outcome. We recommend to closely follow the motor and attentional development of these children.

Functional outcome of very preterm-born and small-for-gestational-age children at school age.

BACKGROUND: Our aim was to determine functional outcome of very preterm-born and small-for-gestational-age (SGA) children as compared with matched controls at school age. METHODS: We included 28 very preterm SGA children (GA <32 wk, birth weight (BW) <10th percentile), born in 2000-2001. We also included 28 very preterm but appropriate-for-gestational-age (AGA) children, matched for GA, gender, and birth year, as controls. We assessed motor skills, intelligence quotient (IQ), attention, verbal memory, visual perception, visuomotor integration, executive functioning, and behavior of both sets of children at school age. RESULTS: The SGA children had a median GA of 29.7 wk and BW of 888 g, whereas the controls had a median GA of 29.4 wk and BW of 1,163 g. At 8.6 y, the median total IQ of the SGA children was 94 as compared with 95 in the controls (not significant). Performance IQ was significantly lower in SGA children (89 vs. 95, P = 0.043), whereas verbal IQ was not (95 vs. 95). Total motor skills (P = 0.048) and fine motor skills (P = 0.021) were worse in SGA children. Furthermore, SGA children scored lower on selective attention (P = 0.026) and visual perception (P = 0.025). Other scores did not differ significantly between groups. CONCLUSION: The differences we found between the groups were small. This suggests that the impaired functioning of very preterm-born SGA children is attributable to their having been born very preterm rather than to being SGA.

Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period.

BACKGROUND: Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). OBJECTIVE: To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. DESIGN/METHODS: We included 82 children (born 1998-2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP). RESULTS: Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e., death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98-7.69; P=.055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42-32.82, P=.016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90-5.36; P<.001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99-32.97, P=.051. We found no association between seizure aetiology and outcome. CONCLUSIONS: In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.

Tractography of the corticospinal tracts in infants with focal perinatal injury: comparison with normal controls and to motor development.

INTRODUCTION: Our aims were to (1) assess the corticospinal tracts (CSTs) in infants with focal injury and healthy term controls using probabilistic tractography and (2) to correlate the conventional magnetic resonance imaging (MRI) and tractography findings in infants with focal injury with their later motor function. METHODS: We studied 20 infants with focal lesions and 23 controls using MRI and diffusion tensor imaging. Tract volume, fractional anisotropy (FA), apparent diffusion coefficient (ADC) values, axial diffusivity and radial diffusivity (RD) of the CSTs were determined. Asymmetry indices (AIs) were calculated by comparing ipsilateral to contralateral CSTs. Motor outcome was assessed using a standardized neurological examination. RESULTS: Conventional MRI was able to predict normal motor development (n = 9) or hemiplegia (n = 6). In children who developed a mild motor asymmetry (n = 5), conventional MRI predicted a hemiplegia in two and normal motor development in three infants. The AIs for tract volume, FA, ADC and RD showed a significant difference between controls and infants who developed a hemiplegia, and RD also showed a significant difference in AI between controls and infants who developed a mild asymmetry. CONCLUSION: Conventional MRI was able to predict subsequent normal motor development or hemiplegia following focal injury in newborn infants. Measures of RD obtained from diffusion tractography may offer additional information for predicting a subsequent asymmetry in motor function.

Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: follow-up of two randomised controlled trials.

OBJECTIVE: Free-radical-induced reperfusion injury has been recognised as an important cause of brain tissue damage after birth asphyxia. Allopurinol reduces the formation of free radicals, thereby potentially limiting the amount of hypoxia-reperfusion damage. In this study the long-term outcome of neonatal allopurinol treatment after birth asphyxia was examined. DESIGN: Follow-up of 4 to 8 years of two earlier performed randomised controlled trials. SETTING: Leiden University Medical Center, University Medical Center Groningen and University Medical Center Utrecht, The Netherlands. PATIENTS: Fifty-four term infants were included when suffering from moderate-to-severe birth asphyxia in two previously performed trials. INTERVENTION: Infants either received 40 mg/kg allopurinol (with an interval of 12 h) starting within 4 h after birth or served as controls. MAIN OUTCOME MEASURES: Children, who survived, were assessed with the Wechsler Preschool and Primary Scales of Intelligence test or Wechsler Intelligence Scale for Children and underwent a neurological examination. The effect of allopurinol on severe adverse outcome (defined as mortality or severe disability at the age of 4-8 years) was examined in the total group of asphyxiated infants and in a predefined subgroup of moderately asphyxiated infants (based on the amplitude integrated electroencephalogram). RESULTS: The mean age during follow-up (n=23) was 5 years and 5 months (SD 1 year and 2 months). There were no differences in long-term outcome between the allopurinol-treated infants and controls. However, subgroup analysis of the moderately asphyxiated group showed significantly less severe adverse outcome in the allopurinol-treated infants compared with controls (25% vs 65%; RR 0.40, 95%CI 0.17 to 0.94). CONCLUSIONS: The reported data may suggest a (neuro)protective effect of neonatal allopurinol treatment in moderately asphyxiated infants.

Neurodevelopmental outcome in preterm infants.

AIM: To determine the distribution of cognitive and motor scores in preterm children, and to establish the influence of brain lesions and decreasing gestational age thereon. METHOD: One hundred and six very preterm children (63 males, 43 females; gestational age 24.0-31.6 wk; birthweight 480-2275 g) were assessed for cognition and motor outcome at 6 to 12 years. We assessed total, verbal, and performance IQ using the Wechsler Intelligence Scale for Children, and motor outcome using the Movement Assessment Battery for Children (Movement ABC). RESULTS: The IQs and Movement ABC z-scores were normally distributed, but shifted to the left. Mean total IQ (SD) was 91 (12), performance IQ 89 (13), and verbal IQ 93 (15), being 0.60, 0.73, and 0.47 SD lower than the norm respectively. Movement ABC z-scores were -1.27 SD lower (SD 1.01). IQ and Movement ABC z-scores did not correlate with brain lesions or gestational age. INTERPRETATION: The distribution curve for cognition and motor outcome at school age is shifted to the left in preterm children, with an effect size of 0.60 SD for IQ (nine IQ points) and 1.27 SD for motor outcome. These findings are restricted to the current group. Developmental disruptions, affecting cerebral white matter, cortex, cerebellum, and thalamus might be involved, although the exact pathogenetic mechanism is unclear.

Functional impairments at school age of children with necrotizing enterocolitis or spontaneous intestinal perforation.

We aimed to determine motor, cognitive, and behavioral outcome at school age of children who had either necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP). This case-control study included infants with NEC Bell's stage IIA onward, infants with SIP, and matched controls (1996-2002). At school age, we assessed motor skills, intelligence, visual perception, visuomotor integration, verbal memory, attention, behavior, and executive functions. Of 93 infants with NEC or SIP, 28 (30%) died. We included 52 of 65 survivors for follow-up. At mean age of 9 y, we found that 68% of the children had borderline or abnormal scores on the Movement Assessment Battery for Children (versus 45% of controls). Their mean total intelligence quotient (IQ) was 86 ± 14 compared with 97 ± 9 in the controls. In addition, attention and visual perception were affected (p < 0.01 and p = 0.02). In comparison to controls, surgically treated children were at highest risk for adverse outcome. In conclusion, at school age, the motor functions and intelligence of many children with NEC or SIP were borderline or abnormal and, specifically, attention and visual perception were impaired. Children with NEC or SIP form a specific risk group for functional impairments at school age even though the majority does not have overt brain pathology.

Functional impairments at school age of preterm born children with late-onset sepsis.

BACKGROUND: Late-onset sepsis is a relatively common complication particularly of preterm birth that affects approximately a quarter of very low birth weight infants. AIM: We aimed to determine the motor, cognitive, and behavioural outcome at school age of preterm children with late-onset sepsis compared to matched controls. STUDY DESIGN AND SUBJECTS: A prospective case-control study that included preterm infants (gestational age<32weeks and/or birth weight<1500g) admitted to our Neonatal Intensive Care Unit in 2000-2001 with a culture-proven late-onset sepsis, and controls matched for gestational age. OUTCOME MEASURES: At school age we assessed motor skills, intelligence, visual perception, visuomotor integration, verbal memory, attention, executive functioning, and behaviour. RESULTS: At 6-9years, 21 of 32 children with late-onset sepsis (68%) had borderline or abnormal motor outcome with most problems in fine motor skills. Their total IQ was 89 compared to 98 in controls. In addition, verbal memory and attention were affected compared to controls (0.61 standard deviations (SD), 95% confidence interval (CI) 0.04-1.17, p=0.033 and 0.94 SD, 95% CI 0.32-1.62, p=0.011, respectively). Multiple episodes of sepsis and gram-negative sepsis were risk factors for worse cognitive outcome. CONCLUSIONS: At school age, a majority of preterm children with late-onset sepsis had motor problems. Their IQ was considerably lower than matched controls, and memory and attention were specifically impaired. Outcome at school age of preterm children with late-onset sepsis was worse than previously thought.

Developmental trajectories from birth to school age in healthy term-born children.

OBJECTIVE: To determine the stability of the scores obtained on tests of motor development from birth until school age in healthy, term singletons and to determine if early motor scores are associated with more complex cognitive functions at school age, such as attention and memory. PATIENTS AND METHODS: This longitudinal, prospective cohort study included 77 infants. The motor development of these infants was assessed during the neonatal period with Prechtl's neurologic examination; in early infancy with Touwen's neurologic examination and general movement assessment; at toddler age with Hempel's neurologic examination and the Psychomotor Developmental Index from the Bayley Scales of Infant Development; and at school age with the Movement Assessment Battery for Children. Cognition was determined at toddler age with the Mental Developmental Index from the Bayley Scales of Infant Development; and at school age with an intelligence test and attention and memory tests. RESULTS: The mean absolute difference in standardized motor scores for all time points was 1.01 SD (95% confidence interval: 0.91-1.11). Only the explained proportions of variance of maternal socioeconomic status and verbal intelligence were significant for sustained attention and verbal memory (r(2) = 0.104, P = .030 and r(2) = 0.074, P = .027), respectively. The children's scores on early motor tests added little value for their motor and cognitive development at school age. CONCLUSIONS: In healthy children the stability of motor development from birth until school age is low. Maternal socioeconomic status and verbal intelligence rather than the infants' scores on early motor tests signified added value for complex cognitive functions at school age.

Functional outcome at school age of preterm infants with periventricular hemorrhagic infarction.

OBJECTIVES: Our objective was to determine motor, cognitive, and behavioral outcome at school age in preterm children with periventricular hemorrhagic infarction and to identify cerebral risk factors for adverse outcome. METHODS: This was a prospective cohort study of all preterm infants who were <37 weeks' gestation, had periventricular hemorrhagic infarction, and were admitted between 1995 and 2003. Ultrasound scans were reviewed for characteristics of periventricular hemorrhagic infarction and other cerebral abnormalities. At 4 to 12 years of age, motor outcome was assessed by the Gross Motor Function Classification System and the Manual Ability Classification System, by a neurologic examination (Touwen), an intelligence test (Wechsler Intelligence Scale III/Wechsler Preschool and Primary Scale of Intelligence-Revised), and tests for visual-motor integration, visual perception, and verbal memory. Behavior was assessed by using the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. RESULTS: Of 38 infants, 15 (39%) died. Twenty-one of the 23 survivors were included in the follow-up. Four infants were neurologically normal, 1 had minor neurologic dysfunction, 13 had unilateral spastic cerebral palsy, and 3 had bilateral cerebral palsy. Coordination, associated movements, and fine manipulative abilities were affected most according to the neurologic examination. Gross Motor Function Classification System scores were level 1 (7 children), level 2 (7 children), level 3 (1 child), and level 4 (2 children). Manual Ability Classification System scores were normal (4 children), level 1 (8 children), level 2 (7 children), and level 3 (2 children). The mean and median total IQ was 83. Visual perception was normal in 88% of children, visuomotor integration was normal in 74%, and verbal memory was normal in 50%. Behavior was normal in 53% of children, and executive functions were normal in 65% and 29% of children (by parent and teacher report, respectively). Characteristics of the periventricular hemorrhagic infarction were not related to functional motor outcome and intelligence. Posthemorrhagic ventricular dilatation was a risk factor for poorer total and performance intelligence and abnormal fine manipulative abilities. CONCLUSIONS: The majority of surviving preterm children with periventricular hemorrhagic infarction had cerebral palsy with limited functional impairment at school age. Intelligence was within 1 SD of the norm of preterm children without lesions in 60% to 80% of the children. Verbal memory, in particular, was affected. Behavioral and executive function problems occurred slightly more than in preterm infants without lesions. The functional outcome at school age of preterm children with periventricular hemorrhagic infarction is better than previously thought.

Prenatal exposure to organohalogens, including brominated flame retardants, influences motor, cognitive, and behavioral performance at school age.

BACKGROUND: Organohalogen compounds (OHCs) are known to have neurotoxic effects on the developing brain. OBJECTIVE: We investigated the influence of prenatal exposure to OHCs, including brominated flame retardants, on motor, cognitive, and behavioral outcome in healthy children of school age. METHODS: This study was part of the prospective Groningen infant COMPARE (Comparison of Exposure-Effect Pathways to Improve the Assessment of Human Health Risks of Complex Environmental Mixtures of Organohalogens) study. It included 62 children in whose mothers the following compounds had been determined in the 35th week of pregnancy: 2,2'-bis-(4 chlorophenyl)-1,1'-dichloroethene, pentachlorophenol (PCP), polychlorinated biphenyl congener 153 (PCB-153), 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4OH-CB-107), 4OH-CB-146, 4OH-CB-187, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), BDE-99, BDE-100, BDE-153, BDE-154, and hexabromocyclododecane. Thyroid hormones were determined in umbilical cord blood. When the children were 5-6 years of age, we assessed their neuropsychological functioning: motor performance (coordination, fine motor skills), cognition (intelligence, visual perception, visuomotor integration, inhibitory control, verbal memory, and attention), and behavior. RESULTS: Brominated flame retardants correlated with worse fine manipulative abilities, worse attention, better coordination, better visual perception, and better behavior. Chlorinated OHCs correlated with less choreiform dyskinesia. Hydroxylated polychlorinated biphenyls correlated with worse fine manipulative abilities, better attention, and better visual perception. The wood protective agent (PCP) correlated with worse coordination, less sensory integrity, worse attention, and worse visuomotor integration. CONCLUSIONS: Our results demonstrate for the first time that transplacental transfer of polybrominated flame retardants is associated with the development of children at school age. Because of the widespread use of these compounds, especially in the United States, where concentrations in the environment are four times higher than in Europe, these results cause serious concern.