Structural brain maturation differs between preterm and term piglets, whereas brain activity does not.

AIM: The aim of the study was to investigate whether amplitude-integrated electroencephalography (aEEG) and cerebral magnetic resonance imaging (MRI) in preterm piglets would provide measures of cerebral functional, microstructural and anatomical maturation, which might reflect the signs of functional brain immaturity, documented in preterm piglets. METHODS: During July-October 2013 at the NEOMUNE Centre, Copenhagen University, Denmark, 31 preterm (90% gestation) and 10 term piglets underwent aEEG on days 1, 2, 4 and 11, and MRI on day 25. Physical activity levels were recorded. RESULTS: Preterm showed delayed neonatal arousal and physical activity, relative to term piglets. Preterm piglets had lower growth rates and brain volume than term piglets, but aEEG patterns were similar. MRI mean diffusivity was also similar, but fractional anisotropy (FA) was lower in preterm piglets (p < 0.001). CONCLUSION: Functional brain maturation, as assessed by aEEG, was relatively advanced in preterm piglets. Conversely, the low FA in the preterm piglets suggests that the white matter microstructure remains less mature in preterm compared to term piglets at postnatal day 25. The results might be utilised to define whether and how preterm piglets may contribute to preclinical models for brain development in preterm infants.

Short-term lower leg growth in asthmatic children treated with inhaled beta2-agonists.

BACKGROUND: Knemometry studies of growth suppressive effects of inhaled glucocorticoids in children with asthma usually allow participating children to use concomitant inhaled beta2-agonists. Systemic beta2-agonists, however, have been found to suppress growth hormone secretion and this has caused concern about a possible confounding effect of inhaled beta2-agonists on results of growth studies of exogenous glucocorticoids. AIM: The study evaluated whether inhaled salbutamol adversely affects short-term growth. SUBJECTS AND METHODS: Fifteen children aged 6-12 years with mild asthma were enrolled in a single-blind, randomized crossover study with two 2-week treatment periods and a 1-week run-in. During the active period treatment dry powder salbutamol (Ventoline Diskhaler) 200 microg was inhaled three times a day. During the comparative period no treatment was given. Knemometry of the right lower leg was performed on the first and the last day of each period. RESULTS: Mean lower leg growth rates (SEM) during no-treatment and salbutamol periods were 0.35 (0.06) and 0.42 (0.07) mm per week, respectively (P = 0.35, t = -0.98, 95% CI: 0.25-0.93 mm per week). CONCLUSIONS: Inhaled salbutamol 200 microg three times daily does not suppress short-term growth in asthmatic children. Inhaled beta2-agonists in equipotent doses and regimens can be safely used in short-term knemometric growth studies of exogenous glucocorticoids without any risk of confounding the results.

Methodological aspects of high-frequency ultrasound of skin in children.

BACKGROUND: High-frequency ultrasound of the skin has recently been introduced for assessment of systemic effects in the cutis and subcutis of oral and inhaled glucocorticoids in children. However, the use of high-frequency skin ultrasound in clinical trials is invalidated because important methodological aspects have not been addressed. The aim of the present study was to evaluate inter- and intraobserver, day to day and diurnal variations of measurement of thickness of cutis and subcutis, and the fraction of low echogenic pixels (fLEP) in the cutis and, furthermore, to assess effects of exercise on the cutis and subcutis and variations in subcutaneous thickness between anatomical locations in children with a high-frequency B-mode ultrasound scanning device. METHODS: Three studies were conducted, each including 10 healthy prepubertal children. High-frequency skin ultrasound was performed with the 20 MHz Dermascan C (Cortex Technology, Hadsund, Denmark). In study 1, the same observer performed five consecutive scannings to assess intraobserver variations. In study two different observers performed scannings at 2 h intervals between 08:00 and 20:00 h, whereby interobserver and diurnal variations were assessed. In study 3, the same observer performed scannings in different anatomical locations on five consecutive days, and on one of these days before and after exercise. Thus day-to-day variations and the effect of exercise were assessed. RESULTS: Low inter- and intraobserver variations were found on assessment of the thickness of cutis and subcutis, whereas high variations were found on evaluation of the dermal water content. Diurnal variations were absent, and day-to-day variations were low. Exercise caused significant increases in the thickness of cutis and subcutis on the thigh. CONCLUSION: Low inter- and intraobserver variations make high-frequency ultrasound a precise and reliable tool for assessment of the cutaneous and subcutaneous thickness in children. In future trials, repetitive scannings need not to be performed at the same time of the day, whereas strenuous physical activity should be avoided on days of examination.

Lower leg growth suppression caused by inhaled glucocorticoids is not accompanied by reduced thickness of the cutis or subcutis.

BACKGROUND: Exogenous glucocorticoids suppress short-term lower leg growth in children as assessed by knemometry. The knemometric measurements, however, may be confounded by reductions in the thickness of the cutis and subcutis over the knee. AIM: To assess whether inhaled glucocorticoid-induced suppression of short-term growth is accompanied by changes in the thickness of the cutis and subcutis. METHODS: The study was a randomized, controlled, crossover trial with 1 wk treatment, run-in and washout periods. Active treatment was inhaled budesonide 200 microg twice daily. Short-term growth was assessed by knemometry, and the thickness of the cutis and subcutis over the knee, on the volar forearm and abdomen was measured by 20 MHz B-mode ultrasound. MATERIAL: Nineteen children with asthma aged 7 to 13 y. RESULTS: Lower leg growth was significantly reduced during budesonide treatment (0.27 mm/wk) compared to the treatment-free period (0.54 mm/wk) (p = 0.02, 95%: -0.50 to -0.05). Variations in the thickness of the cutis were seen during budesonide treatment (mean +/- SEM): -0.01 +/- 0.03 mm over the knee, -0.02 +/- 0.02 mm on the forearm and 0.01 +/- 0.02 mm on the abdomen. The variations in the total thickness of the cutis and subcutis were -0.05 +/- 0.12 mm, 0.06 +/- 0.12 mm and -0.06 +/- 0.10 mm during budesonide treatment. The variations in thickness of the cutis or subcutis were not statistically different during budesonide treatment and the treatment free period in any anatomical location. CONCLUSIONS: Short-term lower leg growth suppression induced by inhaled glucocorticoids is not confounded by variations in thickness of cutis or subcutis. The present observations further establishes knemometry as a reliable tool for assessment of the risk of growth suppression of inhaled glucocorticoids in children with asthma.