K. C. Ma

Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants

Objectives: A proportion of preterm, very low birthweight (VLBW, < 1500 g) infants may show inadequate adrenal response to stress in the immediate postnatal period. The human corticotrophin releasing hormone (hCRH) stimulation test was used to: (a) determine the relation between pituitary-adrenal response and systemic blood pressure in these infants; (b) characterise the endocrinological features of transient adrenocortical insufficiency of prematurity (TAP). Study design: A total of 226 hCRH tests were performed on 137 VLBW infants on day 7 and 14 of life in a tertiary neonatal centre. Results: Basal, peak, and incremental rise in serum cortisol (ΔCort0–30) on day 7 were associated significantly with the lowest systolic, mean, and diastolic blood pressures recorded during the first two weeks of life (r > 0.25, p < 0.005). These cortisol concentrations also correlated significantly but negatively with the maximum and total cumulative dose of dopamine (r > −0.22, p < 0.02), dobutamine (r > −0.18, p < 0.04), and adrenaline (r > −0.26, p < 0.004), total volume of crystalloid (r > −0.22, p < 0.02), and duration of inotrope treatment (r > −0.25, p < 0.006). Multivariate regression analysis of significant factors showed that the lowest systolic, mean, and diastolic blood pressures remained independently associated with serum cortisol (basal, peak, and ΔCort0–30) on day 7. Hypotensive infants requiring inotropes (group 2) were significantly less mature and more sick than infants with normal blood pressure (group 1). The areas under the ACTH response curves were significantly greater in group 2 than in group 1, on both day 7 (p = 0.004) and day 14 (p = 0.004). In contrast, the area under the cortisol response curve was significantly greater in group 1 than in group 2 on day 7 (p = 0.001), but there was no significant difference between the two groups on day 14. In addition, serum cortisol at the 50th centile in hypotensive infants had high specificity and positive predictive value (0.80–0.93 and 0.81–0.89 respectively) for predicting early neonatal hypotension. Conclusions: This study characterises the fundamental endocrinological features of TAP: normal or exaggerated pituitary response; adrenocortical insufficiency; good recovery of adrenal function by day 14 of postnatal life. The results also provide the centiles of serum cortisol for hypotensive patients and infants with normal blood pressure, and show a significant relation between serum cortisol and blood pressure in VLBW infants.

Refractory hypotension in preterm infants with adrenocortical insufficiency

Five preterm, very low birthweight infants with severe hypotension and adrenocortical insufficiency are described. The profound hypotension was resistant to volume expansion and inotrope treatment, but responded promptly to corticosteroid treatment. A human corticotrophin releasing hormone (hCRH) test performed before corticosteroid treatment showed adequate pituitary response, and the endocrine dysfunction was identified at the adrenal level. Corticosteroid treatment should be considered and could be life saving in severely hypotensive preterm infants who do not respond to conventional treatment with volume expanders and inotropes.

Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children.

Chemokines are responsible for the trafficking of leukocytes to sites of inflammation. Serum chemokine levels were previously shown to be increased in adult patients with atopic dermatitis (AD). We tested whether serum concentrations of chemokines, including macrophage‐derived chemokine (MDC), thymus and activation‐regulated chemokine (TARC), eotaxin (EOX), interferon gamma inducible protein 10 (IP‐10) and monocyte chemotactic protein 1 (MCP‐1), are useful inflammatory markers for assessing AD severity in infants and young children. To investigate this, we assessed the severity of AD clinically using the SCORing Atopic Dermatitis (SCORAD) index system. Serum chemokine concentrations were determined by sandwich enzyme immunoassay. Twenty AD patients with a median age of 2.1 years [interquartile range (IQR): 0.6–4.2] were recruited. Their SCORAD score was 23.5 (12.5–33.5). Serum concentrations of MDC, TARC, EOX, IP‐10 and MCP‐1 were 2551 (1978–3935), 1469 (1125–3070), 68 (57–85), 126 (101−226) and 518 (419–614) pg/ml, respectively. Serum MDC levels correlated with SCORAD (r = 0.608, p = 0.004) and its extent (r = 0.629, p = 0.003) and intensity (r = 0.557, p = 0.011) components. Serum TARC concentration showed weaker correlation with extent (r = 0.474, p = 0.035) and intensity (r = 0.465, p = 0.039) of skin involvement but not SCORAD. The median serum levels of MDC (3131 vs. 2394 pg/ml; p = 0.031) and EOX (80 vs. 61 pg/ml; p = 0.046) were also higher in children with moderate as compared with mild AD. The other chemokines did not correlate with AD severity. In conclusion, our results suggest that serum MDC concentration may be a useful inflammatory marker for assessing AD severity in infants and young children.

Validation of a self-administered questionnaire in Chinese in the assessment of eczema severity.

Abstract:  The purpose of this study was to validate the Chinese version of the Nottingham Eczema Severity Score (NESS) in determining the severity of atopic dermatitis (AD). Each parent or patient filled out a questionnaire in Chinese based on the NESS. A physician then repeated the NESS independently. Finally, the severity of AD was evaluated according to the Scoring Atopic Dermatitis (SCORAD) scale. The NESSs, severity grades, and SCORAD were analyzed for agreement and correlation. The severity grading agreed with the physicians grading in 38 of 52 parents (73%) and in 16 of 18 children (89%) who self‐evaluated the severity of their AD. The weighted kappa (95% confidence interval [CI]) for parents with children less than 10 years old, parents with children ≥10 years old, and patients who self‐evaluated their AD were 0.79 (0.66–0.91), 0.85 (0.69–1.00), and 0.74 (0.36–1.00), respectively. The R2 for the NESS by parents, the NESS by patients, and the SCORAD scores was 42.1%, 47.5%, and 49.8%, respectively. When compared with the parents, the older children who self‐evaluated their AD showed a better correlation of the NESS with the SCORAD index. The self‐administered questionnaire appears to be useful in assessing AD severity in Chinese children.

A survey of traditional Chinese medicine use in children with atopic dermatitis attending a paediatric dermatology clinic

Use of traditional Chinese medicine (TCM) for various paediatric diseases has been popular. Often, parents or caregivers believe that herbs possess therapeutic effects without any harmful consequence. This fallacy is especially prevalent in the caregivers of children with chronic diseases such as atopic dermatitis (AD). We interviewed 227 consecutive children with AD to assess the attitudes of the caregivers to TCM use, based on a 14‐item questionnaire. Of these respondents, 67 (30%) admitted that the child had been given TCM in the past 12 months, one‐third of these were currently taking TCM and one‐quarter had used TCM for 6 months or more. TCM was prescribed by a Chinese medicine practitioner in 63 patients (94%), and herbal tea/soup was the commonest TCM taken. The majority (94%) had not been told of any possible side effects of TCM. Nearly 60% thought that TCM helped to improve their childs AD. Respondents for children with severe eczema were less likely to think that TCM helped to improve their childs eczema than those with mild or moderate eczema. TCM use was not associated with parental ages or ‘grandparent as caregiver’ but ‘severe AD’ was an independent factor for TCM use (OR 3.24, 95% CI 1.67–6.31; p = 0.0003).

Serum levels of cutaneous T-cell attracting chemokine (CTACK) as a laboratory marker of the severity of atopic dermatitis in children

There are at least 13 scoring systems for the assessment of disease severity in atopic dermatitis (AD). Each system has its problems with interobserver and intraobserver variability. Cutaneous T‐cell attracting chemokine (CTACK) is a skin‐specific chemoattractant which may correlate with AD severity and obviate the issue of observer reliability. We evaluated whether serum CTACK concentrations were associated with the severity of AD in children according to the SCORing Atopic Dermatitis (SCORAD) index. Thirty‐seven Chinese children with AD (23 boys, 14 girls; aged 1–11 years) and 13 controls were recruited. The median (interquartile range) overall SCORAD for AD patients was 29.7 (20.3–49.7). Serum concentrations of CTACK and two other atopy‐related chemokines, macrophage‐derived chemokine (MDC) and thymus and activation‐regulated chemokine (TARC), were measured by sandwich enzyme immunoassay. There were significant correlations between SCORAD (r = 0.394, P = 0.016), its area (r = 0.528, P = 0.001) and intensity components (r = 0.429, P = 0.008) with serum levels of CTACK. The serum concentrations of inflammatory markers MDC and TARC also correlated with the CTACK concentrations (r = 0.618, P < 0.001, and r = 0.587, P = 0.001, respectively). Serum CTACK concentration appears to be a skin‐specific objective marker that correlates with various clinical and laboratory parameters of AD.

A pentaherbs capsule as a treatment option for atopic dermatitis in children: An open-labeled case series

Traditional Chinese Medicine (TCM) has been used in patients with atopic dermatitis (AD), but its therapeutic effects are debatable. We evaluated the clinical and biochemical effects of a TCM capsule (PentaHerbs capsule) in children with AD. After a run-in period of 4 weeks, children old enough to manage oral medication were admitted and their disease severity was evaluated by the SCORing Atopic Dermatitis (SCORAD) index. Blood was obtained for complete blood count, total and allergen-specific immunoglobulin E (IgE), biochemical studies and inflammatory markers of AD severity [serum cutaneous T cell-attracting chemokine (CTACK), macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC) and eosinophil cationic protein (ECP)] prior to, and after 3 months of, TCM use. Three PentaHerbs capsules twice a day were prescribed for 4 months. Patients were followed monthly to ensure compliance, and SCORAD scores were obtained at each visit. Five boys and four girls participated in the study. All patients had detectable food or inhalant-specific IgE in serum. There was significant improvement in the overall and component SCORAD scores. There were no significant differences between the pre- and post-treatment values of the serum CTACK, MDC, TARC and ECP levels but CTACK showed a decreasing trend (p = 0.069). No clinical or biochemical evidence of any adverse drug reaction was observed during the study period. The PentaHerbs capsules were well tolerated by the children and apparent beneficial effects were noted clinically. A larger, randomized placebo-controlled study is required to confirm the efficacy of this formulation for AD.

Effect of multiple courses of antenatal corticosteroids on pituitary-adrenal function in preterm infants.

AIM To evaluate the pituitary–adrenal function of preterm infants whose mothers received multiple courses (8 or more doses) of antenatal dexamethasone. METHODS The pituitary–adrenal function of 14 preterm infants whose mothers received eight or more doses of antenatal dexamethasone were assessed using the human corticotrophin releasing hormone (hCRH) stimulation test when 7 days (n = 14) and 14 days old (n = 12). During each test, blood samples were taken at 0 (baseline), 15, 30 and 60 minutes after an intravenous bolus dose of hCRH (1 μg/kg). The corresponding hormone concentrations were compared between days 7 and 14, and with various associated factors. RESULTS The baseline (0 min) plasma adrenocorticotrophic hormone concentration was significantly higher at day 14 than at day 7 (p = 0.036). None of the corresponding poststimulation (15, 30, and 60 min) hormone concentrations was significantly different between the two time epochs. When the association between the hormone concentrations and the number of antenatal dexamethasone doses received by the mothers was assessed, a significant negative correlation was observed in serum cortisol concentrations at 15 and 30 min on day 14 (r = −0.59, p = 0.04 and r = −0.60, p = 0.039, respectively). CONCLUSIONS The absence of a significant difference in poststimulation hormone concentrations between days 7 and 14 in this cohort of infants, and the similarity of their hormone responses with those of older children and adults, suggests that no severe pituitary–adrenal suppression had occurred. None the less there was evidence of mild adrenal suppression in some of the treated infants. Vigilance in monitoring blood pressure, electrolytes and signs of adrenal suppression in infants whose mothers receive multiple courses (8 or more doses) of antenatal dexamethasone is required, as some of them might have diminished adrenal reserve.

Serum concentration of IL-18 correlates with disease extent in young children with atopic dermatitis.

Abstract:  Interleukin (IL)‐18 is a pleiotropic cytokine that plays an important role in both type 1 (Th1) and type 2 (Th2) helper T lymphocyte‐mediated immunity. Previous studies have suggested that IL‐18 may be an inflammatory marker for atopic dermatitis (AD). The purpose of our study was to test whether the serum concentration of IL‐18 is a useful inflammatory marker for assessing AD severity in young children. Nineteen AD patients with a median age of 2.2 years (interquartile range 0.7–4.6 years) were recruited. The severity of AD was clinically determined using the Scoring Atopic Dermatitis (SCORAD) index. Their SCORAD score was 23.9 (range 18.6–34.8). Serum IL‐18 levels were determined by sandwich enzyme immunoassay. The median serum concentration of IL‐18 was 394 pg/ml (interquartile range 204–612 pg/ml). Serum IL‐18 levels correlated with SCORAD scores (r = 0.502, p = 0.029) and their extent component (r = 0.633, p = 0.004). When compared with mild disease with low SCORAD scores, the serum concentration in moderate to severe disease was significantly higher (p = 0.014). We concluded that serum IL‐18 concentration is elevated in young children with AD. It may be a useful inflammatory marker that correlates with the extent component of AD in particular, and differentiates mild disease from more severe disease when used for assessing AD severity in young children.

Leptin and metabolic hormones in preterm newborns

AIM To investigate the inter-relation between leptin and other metabolic hormones in preterm and term infants and to explore whether a functional “adipoinsular axis” might exist in preterm newborns. METHODS A total of 140 preterm and term newborns were prospectively recruited and categorised according to gestation length. Blood samples were taken at 24 hours (day 1), and on day 4–5 of life. RESULTS Serum leptin, cortisol, free thyroxine, and plasma ACTH on day 1 were significantly higher in term than in preterm infants. The relation between serum leptin and gestation followed a non-linear pattern; the slope of the curve began to increase steeply between 33 and 35 weeks gestation. Serum leptin on day 1 was significantly associated with serum insulin, insulin:glucose ratio, and plasma ACTH in infants less than 34 weeks gestation; serum leptin on day 1 and day 4–5 were significantly correlated with insulin:glucose ratio in infants 34 or more weeks gestation. Significant changes in the pattern of metabolic hormones were observed in the first week of life. Serum insulin and plasma glucose were significantly increased between day 1 and day 4–5; serum leptin was significantly decreased. CONCLUSIONS The circulating leptin concentration increases markedly after 34 weeks gestation and bears a close temporal relation with the exponential accumulation of body fat mass during that period. The inter-relation between serum leptin and insulin or insulin:glucose ratio before and after 34 weeks gestation indicates that the “adipoinsular axis” is likely to be functional in early (<34 weeks gestation) intrauterine life. The rapid decline in the circulating concentrations of leptin after birth may be of physiological advantage to preterm and term newborns by limiting their body energy expenditure and conserving nutritional reverses for subsequent growth and development. Key message Serum leptin increases considerably after 34 weeks gestation and bears a close temporal relation with the rapid accumulation of body fat mass during late gestation. The association between serum leptin and insulin or insulin:glucose ratio suggests that the “adipoinsular axis” is likely to be functional in early (less than 34 weeks gestation) intrauterine life