Microstructural alterations in association tracts and language abilities in schoolchildren born very preterm and with poor fetal growth.

BACKGROUND: Prematurity and perinatal risk factors may influence white matter microstructure. In turn, these maturational changes may influence language development in this high-risk population of children. OBJECTIVE: To evaluate differences in the microstructure of association tracts between preterm and term children and between preterm children with appropriate growth and those with fetal growth restriction and to study whether the diffusion tensor metrics of these tracts correlate with language abilities in schoolchildren with no severe neurological impairment. MATERIALS AND METHODS: This study prospectively followed 56 very preterm children (mean gestational age: 28.7 weeks) and 21 age- and gender-matched term children who underwent diffusion tensor imaging at a mean age of 9 years. We used automated probabilistic tractography and measured fractional anisotropy in seven bilateral association tracts known to belong to the white matter language network. Both groups participated in language assessment using five standardised tests at the same age. RESULTS: Preterm children had lower fractional anisotropy in the right superior longitudinal fasciculus 1 compared to term children (P < 0.05). Preterm children with fetal growth restriction had lower fractional anisotropy in the left inferior longitudinal fasciculus compared to preterm children with appropriate fetal growth (P < 0.05). Fractional anisotropy in three dorsal tracts and in two dorsal and one ventral tract had a positive correlation with language assessments among preterm children and preterm children with fetal growth restriction, respectively (P < 0.05). CONCLUSION: There were some microstructural differences in language-related tracts between preterm and term children and between preterm children with appropriate and those with restricted fetal growth. Children with better language abilities had a higher fractional anisotropy in distinct white matter tracts.

Antenatal and neonatal risk factors in very preterm children were associated with language difficulties at 9 years of age.

AIM: This Finnish study compared language and reading abilities between schoolchildren born at a very low gestational age (VLGA) of <32 weeks and at term and analysed any associations between antenatal and neonatal risk factors and language skills in the VLGA group. METHODS: We prospectively followed 76 children born at a VLGA and 50 children born at term when they reached a mean age of 9.0 (8.1-10.0) years. They attended mainstream schools and had no severe neurosensory disabilities. Receptive language ability, rapid naming and word reading were evaluated using standardised tests. RESULTS: Children in the VLGA group had lower scores for receptive language abilities (median 55.0 vs. 57.0, p = 0.01) and word reading (mean 4.4 vs. 5.1, p = 0.03) than the children in the term group. In the VLGA group, foetal growth restriction was associated with lower scores for rapid naming, early intraventricular haemorrhage was associated with poor word reading and respiratory distress syndrome was associated with poor rapid naming (p < 0.05). CONCLUSION: Schoolchildren born at a VLGA had more difficulties with receptive language abilities and word reading than children born at term. Foetal growth restriction and early neonatal morbidities were associated with language difficulties.

Children born before 32 weeks of gestation displayed impaired reading fluency, comprehension and spelling skills at 9 years of age.

AIM: Our aim was to study whether prematurity, associated with prenatal and neonatal risk factors, affects specific literacy skills among school children born at a very low gestational age (VLGA) of <32 weeks. METHODS: The study group comprised 76 prospectively followed VLGA children born between November 1998 and November 2002 at Oulu University Hospital, Finland, and 51 term controls. The median gestational age of the VLGA children was 29.0 (24.1-31.9) weeks. All children were examined at a median age of 8.9 (8.0-9.9) years in Oulu between November 2007 and November 2011. Reading fluency, comprehension and spelling skills were evaluated using standardised tests for Finnish-speaking children. RESULTS: Very low gestational age children had significantly poorer test results in reading comprehension (median 6.9 vs 8.3, P = .014) and spelling (median 35.7 vs 38.0, P = .013) than term children. Furthermore, VLGA children more often performed below the 10th percentile normal values in spelling (P = .012) compared with term controls. Foetal growth restriction was associated with lower scoring in reading fluency (P = .023) and spelling (P = .004) among VLGA children. CONCLUSION: Very low gestational age school children performed poorer in reading comprehension and spelling than term children. In addition, poor foetal growth in VLGA children was associated with literacy problems.

Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat.

Two catechol-O-methyltransferase (COMT) inhibitors, entacapone and tolcapone, were compared in the rat to elucidate the actual differences between their pharmacokinetics and pharmacodynamics after single and repeated administration. Their inhibitory potencies were also compared in vitro. After intravenous administration (3 mg/kg), the elimination half-life (t(1/2 beta)) of entacapone (0.8 h) was clearly shorter than that of tolcapone (2.9 h). The striatum/serum ratio of tolcapone was 3-fold higher than that of entacapone. After a single oral dose (10 mg/kg), both entacapone and tolcapone produced an equal maximal degree of COMT inhibition in peripheral tissues, but tolcapone inhibited striatal COMT more effectively than did entacapone. After the 7-day treatment (10 mg/kg twice daily), COMT activity had recovered to a level of 67 to 101% of control within 8 h after the last dose of entacapone. In tolcapone-treated animals, there was still extensive COMT inhibition present in peripheral tissues, and the degree of inhibition was higher than that attained after a single dose. The pharmacokinetic-pharmacodynamic modeling revealed that a plateau of COMT inhibition near the maximal attainable inhibition was reached already by plasma concentrations below 2000 ng/ml, both with entacapone and tolcapone. Entacapone and tolcapone inhibited equally rat liver COMT in vitro with K(i) values of 10.7 and 10.0 nM, respectively. In conclusion, tolcapone has a longer duration of action and a better brain penetration than entacapone. The results also suggest that peripheral COMT is inhibited continuously when tolcapone is dosed at 12-h intervals, but this was not seen with entacapone.