Rhona Stephen

Bone and collagen markers in preterm infants: relationship with growth and bone mineral content over the first 10 weeks of life.

In a longitudinal study of 25 preterm infants, we have examined the relationship of bone-specific alkaline phosphatase (ALP), C-terminal propeptide of type I collagen (PICP), N-terminal propeptide of type III procollagen (P3NP), C-terminal telopeptide of type I collagen, urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd), with rates of gain in weight, length, and lower leg length and with bone mineral content (BMC), all measured at weekly intervals over the first 10 wk of life. Concentrations of all collagen markers were 10-fold higher than in older children. Each marker showed a distinctive pattern of postnatal change, with early increases in PICP and P3NP and decreases in ICTP reflecting postnatal growth. Once markers had reached a plateau during weeks 4–10, P3NP was positively correlated, whereas Pyd and Dpd were negatively correlated with rate of weight gain (r= +0.44, −0.46, and −0.40, respectively, p< 0.05). P3NP was also positively correlated with overall linear growth (r= +0.44, p< 0.05). PICP was strongly correlated with mean BMC (r= +0.63, p< 0.01) and with total BMC attained by the end of the study period (r= +0.81, p< 0.001). Bone ALP was positively correlated with the rate of bone mineral accretion (r= +0.55, p= 0.01). We conclude that the marker of soft-tissue collagen formation, P3NP, is a good marker for overall ponderal and linear growth in preterm infants, whereas the markers of collagen breakdown, Pyd and Dpd, have inverse relationships with weight gain. The osteoblast markers, PICP and bone ALP, seem to be good surrogate markers for bone mineralization in preterm infants. Markers may provide information on whole-body turnover of bone and collagen that is complementary to traditional physical measures of growth and bone mineralization.

The bigger the burn, the greater the stress

Data characterizing the endocrine stress response to burn injury in children are sparse. We have measured the levels of the stress hormones arginine vasopressin, catecholamines-adrenaline, noradrenaline and dopamine-atrial natriuretic peptide and hormones of the renin-angiotensin-aldosterone system in admission blood samples taken from 35 children admitted to the burns unit of the regional childrens hospital. Hormone levels were compared with the size of burn injury. With the exception of adrenaline, there were significant positive correlations between vasopressin (r = 0.707, p < 0.0001), plasma renin activity (r = 0.721, P < 0.0001), angiotensin II (r = 0.512, P = 0.002), aldosterone (r = 0.620, P < 0.0001), noradrenaline (r = 0.430, P = 0.0189), dopamine (r = 0.627, P = 0.0024) and percentage burn surface area, and a negative correlation between atrial natriuretic peptide (r = 0.548, P = 0.0008) and burn surface area. It is concluded that the hormones which react to stress are very sensitive to burn injury in children, and that the magnitude of their response is closely related to the size of the burn surface area.

The systemic stress response to thermal injury in children

Thermal injury is extremely stressful, but data characterizing the endocrine stress response to this injury in children are sparse. The objective of this study was to measure the effects of thermal injury on the levels of stress hormones in children and to assess the temporal changes associated with them.

Effects of Dexamethasone Treatment on Bone and Collagen Turnover in Preterm Infants with Chronic Lung Disease

Dexamethasone is used commonly in the treatment of chronic lung disease of prematurity, but there are concerns about possible deleterious effects on growth and bone. Our aim in this study was to examine the effects of dexamethasone treatment on bone and collagen turnover in preterm infants. Bone-specific alkaline phosphatase, the C-terminal propeptide of type I collagen (PICP, reflecting whole-body type I collagen synthesis), and the N-terminal propeptide of type III procollagen (P3NP, reflecting soft tissue collagen turnover), together with the C-terminal telopeptide of type I collagen (ICTP), urinary pyridinoline (Pyd), and deoxypyridinoline (all markers of collagen breakdown) were measured at weekly intervals over the first 12 wk of life in 14 preterm infants with chronic lung disease treated with dexamethasone. Results were expressed as SD scores relative to preterm control infants not treated with dexamethasone. PICP, P3NP, ICTP, and Pyd all showed marked decreases (−2.1 to −3.7 SD scores) during the first week of treatment (p < 0.001), returning to pretreatment levels after stopping dexamethasone. In the group as a whole, these collagen markers were negatively correlated with dexamethasone dose (p < 0.0001); negative correlations were also seen in most individual babies, although the slopes of individual regression lines varied by a factor of 2. Weight gain at 12 wk was correlated with PICP, expressed as the mean SD score over 12 wk for each baby, (r = 0.69, p < 0.01) but not with other markers or cumulative dose of dexamethasone. We conclude that dexamethasone markedly suppressed collagen turnover in preterm infants in a dose-dependent fashion, although some babies were more affected than others. The degree of suppression of type I collagen synthesis was a strong independent predictor of overall weight gain over the first 12 wk of life.

Immunoreactive arginine vasopressin in human fetal and neonatal skeletal muscle

We provide evidence for the presence of arginine vasopressin (AVP) in human fetal and neonatal skeletal muscle using a combination of specific RIA, tangential flow ultrafiltration and reverse-phase HPLC separation. The IR-AVP concentrations are negatively correlated with gestational age (r = -0.75, P less than 0.0001) and range from 1 to 10 pmol/g wet wt at 15 weeks gestation to 0.04 pmol/g wet wt at term. This IR-AVP substance is of low molecular weight (less than 3000 mol. wt), elutes in the same position as standard AVP after HPLC separation and is detected by four different anti-AVP antisera.

Serum CrossLaps Compared with Other Markers of Bone Turnover in Severely Malnourished Children before and after Refeeding

In growing children, bone turnover is generally high. There are several biochemical markers of bone formation and resorption that have been validated in adults by bone histomorphometry and calcium kinetics. Markers of bone formation are all measured in plasma and include bone-specific alkaline phosphatase (ALP), osteocalcin, and the C-terminal propeptide of type I collagen (PICP). Their use as markers of growth and bone formation in children is now well established (1)(2). However, most markers of bone resorption are measured in urine, including total pyridinoline (Pyd) and the more bone-specific deoxypyridinoline (Dpd). The main problems associated with the urinary markers in pediatric practice are high within-individual biological variation and the need for either timed collections (frequently impossible in children) or, for random urine samples, expressing results as a ratio to creatinine. Creatinine is itself subject to biological variation and changes with muscle mass. Dpd:creatinine excretion in children is highly variable (3) and hence relatively insensitive to therapeutic interventions. Until recently, only one commercially available marker of bone resorption could be measured in plasma, the cross-linked telopeptide of type I collagen (ICTP). Plasma ICTP appears to be less sensitive than some of the other markers to changes in bone resorption in certain clinical situations (e.g., bisphosphonate treatment), perhaps because of metabolism by osteoclastic cathepsin K (4). There is now a new marker for bone resorption that can be measured in serum or plasma, serum CrossLapsTM (5), for which we have recently reported pediatric reference data (6). The CrossLaps assay is specific for the amino acid sequence EKAHD-β-GGR where the aspartic acid residue (D) is β-isomerized. It detects only cross-linked degradation products of C-terminal telopeptides of type I collagen and is therefore specific for bone resorption. It has been clinically evaluated in adults in whom changes in CrossLaps were inversely …

Dissociation of osmoregulation from plasma arginine vasopressin levels following thermal injury in childhood

Although the syndrome of inappropriate anti-diuretic hormone secretion has been recognised as a complication associated with burn and other trauma in adults, relatively little is known about its incidence in children. The objective of this study was to investigate whether it is a complication associated with burn injury in children. Plasma and urine levels of arginine vasopressin (anti-diuretic hormone), sodium and osmolality were measured in samples collected from 16 burn-injured children admitted to the burns unit of the regional childrens hospital. No significant correlations were found between plasma vasopressin and plasma sodium or osmolality levels, but there were significant correlations between plasma vasopressin and urine osmolality, 36 (r=0.74, p=0. 009), 60 (r=0.92, p=0.000) and 84 h (r=0.84, p=0.001) after admission, respectively. There were also significant correlations between plasma sodium and plasma osmolality, 24 (r=0.7, p=0.005), 36 (r=0.57, p=0.04) and 84 h (r=0.84, p=0.004) after admission. The data suggest dissociation between the osmolar control of vasopressin secretion and vasopressin levels after burn injury in children, but do not support the incidence of inappropriate secretion of antidiuretic hormone.

The Humoral Blood Pressure (BP) Drive in Thermal Injury 152

Aim: Hypertension is a known complication following thermal injury, increasing morbidity still further. The objective was to examine the relationship of hormones known to affect blood pressure with burns in children.

Normative values of substance P and neurokinin A in neonates

Background Substance P (SP) and neurokinin A (NKA) are neuropeptides that have been researched as pain markers in adults, as they are involved in transmission and modulation of pain signals. There is a potential role for them as neurochemical markers of pain in neonates, but this has never previously been investigated. Aim To establish normative values of SP and NKA in neonates. Methods Longitudinal once-daily morning blood samples were collected over two weeks from 142 neonates, gestation 23–40 weeks. Peptides were extracted, and then quantified using an in-house radioimmunoassay. Infants with presumed painful conditions were excluded. Results SP concentrations ranged from <0.98 to 11.2 pmol/L (median 1.7 pmol/L) and NKA concentrations from <1.95 to 74.6 pmol/L (median 6.0 pmol/L). Gestation and birth weight had no significant correlation with peptide concentrations. Postnatally, there was a gradual rise in median SP during the first three days, which decreased again by day 14. Median NKA showed a similar rise, but was not statistically significant. This postnatal rise and fall were more apparent in preterm infants ≤32 weeks gestation. Conclusions This is the first description of normative values of SP and NKA in neonates. SP and NKA show changes with postnatal age, which are more marked in preterm infants.

Neonatal blood pressure waves are associated with surges of systemic noradrenaline.

Neonatal blood pressure (BP) waves have been linked to neonatal illness. We investigated plasma levels of vasoactive hormones when BP waves were observed. Peak and trough noradrenaline levels correlated with mean BP (p = 0.028). There was no relationship to adrenaline, dopamine or endothelin levels.