Koenraad N.J.A. Van Braeckel

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.

The quality of the early motor repertoire in preterm infants predicts minor neurologic dysfunction at school age.

OBJECTIVE The quality of a childs motor repertoire at age 3 to 4 months postterm is predictive of later cerebral palsy (CP). Its predictive power for minor neurologic dysfunction (MND) is unclear. This study aimed to investigate the predictive value of the quality of the early motor repertoire for the development of MND at school age. STUDY DESIGN We assessed the motor repertoire from video recordings made at 6 to 24 weeks postterm in 82 preterm infants (mean gestational age, 29.7 +/- 1.9 weeks; mean birth weight, 1183 +/- 302 g). At age 7 to 11 years, Touwens neurologic examination was performed, and the children were classified as normal (n = 49; 60%), MND (n = 18; 22%), or CP (n = 15; 18%). RESULTS Multiple logistic regression analysis showed that the quality of fidgety movements (FMs) and the quality of the concurrent motor repertoire had independent prognostic value for MND at school age. Abnormal FMs evolved into MND in 64% of the children. Nine of the 28 children with normal FMs and an abnormal concurrent motor repertoire developed abnormally (32%). Only 1 child of the 21 children with normal FMs and a normal concurrent motor repertoire developed MND (5%). CONCLUSIONS Assessment of the quality of the early motor repertoire can accurately identify individual infants at high and low risk for MND at school age.

The early motor repertoire of children born preterm is associated with intelligence at school age.

OBJECTIVE: The goal was to determine whether the quality of general movements (GMs) for preterm children had predictive value for cognitive development at school age. METHODS: In this prospective cohort study, 60 preterm infants (gestational age, median: 30.0 weeks [range: 25–33 weeks]; birth weight, median: 1130 g [range: 595–1800 g]) without cerebral palsy were studied. The quality of GMs was assessed prospectively as normal or abnormal, from video recordings that were made at regular intervals until 17 weeks after term. At 7 to 11 years, intelligence was tested by using the Wechsler Intelligence Scale for Children III, Dutch version. Total IQ (TIQ), verbal IQ (VIQ), and performance IQ (PIQ) scores were calculated. RESULTS: The median TIQ was 93 (range: 67–113), VIQ 96 (range: 68–117), and PIQ 92 (range: 65–119). Fifteen children (25%) had low TIQ scores (<85). When the quality of GMs normalized before 8 weeks after term, TIQ, VIQ, and PIQ scores were in the normal range. Consistently abnormal GMs to 8 weeks after term were associated with lower TIQ, VIQ, and PIQ scores. With correction for male gender and the educational levels of the parents, the likelihood ratio of consistently abnormal GMs for a low TIQ was 4.9 (95% confidence interval: 1.3–17.6). The model explained 22.4% of the variance. CONCLUSIONS: The quality of GMs during the early postterm period is a marker for intelligence at school age. Abnormal GMs during the early postterm period may reflect injury or developmental disruptions of brain areas involved in cognitive development.

Cerebral Oxygenation in Preterm Infants With Germinal Matrix-Intraventricular Hemorrhages

Background and Purpose— Preterm infants are at risk of developing germinal matrix hemorrhages–intraventricular hemorrhages (GMH-IVH). Disturbances in cerebral perfusion are associated with GMH-IVH. Regional cerebral tissue oxygen saturation (rcSO2), measured with near-infrared spectroscopy, and fractional tissue oxygen extraction (FTOE) were calculated to obtain an indication of cerebral perfusion. Our objective was to determine whether rcSO2 and FTOE were associated with GMH-IVH in preterm infants. Methods— This case–control study included 17 preterm infants with Grade I to III GMH-IVH or periventricular hemorrhagic infarction (median gestational age, 29.4 weeks; range, 25.4 to 31.9 weeks; birth weight, 1260 g; range, 850 to 1840 g). Seventeen preterm infants without GMH-IVH, matched for gestational age and birth weight, served as control subjects (gestational age, 29.9 weeks; range, 26.0 to 31.6 weeks; birth weight, 1310 g; range, 730 to 1975 g). RcSO2 and transcutaneous arterial oxygen saturation were measured during 2 hours on Days 1 to 5, 8, and 15 after birth. FTOE was calculated as FTOE=(transcutaneous arterial oxygen saturation−rcSO2)/transcutaneous arterial oxygen saturation. Results— Multilevel analyses showed that rcSO2 was lower and FTOE higher in infants with GMH-IVH on Days 1, 2, 3, 4, 5, 8, and 15. The largest difference occurred on Day 5 with rcSO2 median 64% in infants with GMH-IVH versus 77% in control subjects and FTOE median 0.30 versus 0.17. RcSO2 and FTOE were not affected by the grade of GMH-IVH. Conclusions— Preterm infants with GMH-IVH had lower rcSO2 and higher FTOE during the first 2 weeks after birth irrespective of the grade of GMH-IVH. This suggests that cerebral perfusion is decreased persistently for 2 weeks in infants with GMH-IVH, even in the presence of mild hemorrhages.

Functioning of 7-Year-Old Children Born at 32 to 35 Weeks’ Gestational Age

OBJECTIVE: To compare neuropsychological functions in moderately preterm (32–35 weeks’ gestation) and full-term children at the age of 7 years and identify gender differences. METHODS: Community-based prospective cohort study of 248 moderately preterm children (138 boys) and 130 full-term children (58 boys). Neuropsychological tests included IQ, memory, attention, visual perception, motor skills, visuomotor skills, and parental report of executive functioning. RESULTS: The moderately preterm group performed significantly worse on total and performance IQ, visuospatial reasoning, attention control, inhibition, and executive functioning. No differences were found in verbal IQ, verbal memory, and visuomotor and motor skills. Preterm children were at higher risk for scores <10th percentile on intelligence, visuospatial reasoning (relative risk ratio both: 1.69 [95% confidence interval: 1.29–2.28]), and executive functioning problems (relative risk: 1.94 [95% confidence interval: 1.51–2.57]). Using gender-specific norms, preterm boys performed significantly worse than full-term boys on visuospatial reasoning (P < .01); preterm girls performed significantly worse than full-term girls on visuospatial reasoning, intelligence, attention, and executive functioning (P < .05). CONCLUSIONS: Moderately preterm birth is associated with lower intelligence and poorer neuropsychological functioning at early school age. No differences in motor skills and verbal memory were found. Using gender-specific norms, our data suggest that moderately preterm boys catch up, whereas moderately preterm girls lag behind their peers on various neuropsychological functions by the age of 7 years.

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.

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.

Less efficient elementary visuomotor processes in 7- to 10-year-old preterm-born children without cerebral palsy: An indication of impaired dorsal stream processes

Follow-up studies of preterm children without serious neurological complications have consistently found deficits in visuomotor skills. To determine whether these deficits may be related to impaired elementary visuomotor processes, we investigated movement programming and execution of simple pointing movements in 7- to 10-year-old preterm (<34 weeks g.a. and/or b.w. <1800 g) and full-term children. Such detailed analysis of simple pointing movements provides information on the extent to which processes associated with dorsal and/or cerebellar functions are impaired. Multi-level analysis showed that movement programming and execution were slowed in the 7-, 9-, and 10-year-old preterm groups. This indicates impaired dorsal visual stream functioning in preterm children, but do not rule out impaired cerebellar functioning. At 8 years of age, there were no differences between the two groups in movement execution time. This could have reflected a transition in the development of movement control in the control group, which has been associated in typically developing children with a decrease in motor speed. Interestingly, a similar decrease was not found in the preterm group at 8 years of age.

Cerebral oxygenation is associated with neurodevelopmental outcome of preterm children at age 2 to 3 years

The aim of the study was to determine whether regional cerebral tissue oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE), using near‐infrared spectroscopy, are associated with neurodevelopmental outcome of preterm infants.

Difference rather than delay in development of elementary visuomotor processes in children born preterm without cerebral palsy: a quasi-longitudinal study.

Follow-up studies of preterm children without serious neonatal medical complications have consistently found poor visuomotor and visuospatial skills. In the first round of current follow-up study, we found a deficit in elementary visuomotor processes in preterm children without Cerebral Palsy (CP). To determine whether the development of these processes was delayed or different, we carried out a quasi-longitudinal study in which kinematic characteristics of pointing movements in 7- to 11-year-old preterm born children without CP and in an age-matched full-term group were analyzed. Multi-level analysis suggested a difference rather than a delay in the preterm born group: we found a regression around 8 years of age in the control but not in the preterm group. To our knowledge, this study is the first to provide longitudinal data confirming this regression in the development of movement control in typically developing children. Our results are also consistent in suggesting that elementary visuomotor processes are less efficient in preterm born children without CP: their movements were either slower or less accurate. While these differences were subtle, they persisted until 11 years of age.