Paediatrics (RCH) - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 55
-
ItemPrevalence and determinants of antibiotic exposure in infants: A population-derived Australian birth cohort study(WILEY, 2017-10)AIM: The aim of this study was to describe antibiotic exposure in Australian infants during the first year of life, focusing on antibiotic class, indication, risk factors associated with exposure and comparison with international counterparts. METHODS: The Barwon Infant Study is a birth cohort study (n = 1074) with an unselected antenatal sampling frame from a large regional centre in Victoria, Australia. Longitudinal data on infection and medication were collected at 1, 3, 6, 9 and 12 months by parental questionnaire and from general practitioner and hospital records. Predictors of questionnaire non-completion were identified. A total of 660 infants with complete serial data were comprehensively examined. Antibiotic exposure was calculated as (i) antibiotic prescriptions and (ii) antibiotic days-exposed per person-year. RESULTS: Mean antibiotic prescription rate was 0.92 prescriptions (95% confidence interval (CI), 0.83-1.02) per person-year, with the highest rates in those aged <1 month (1.50 (95% CI, 1.09-1.91) per person-year). A total of 50.0% of infants were exposed to at least one antibiotic in their first year of life. Increasing number of siblings was associated with increased antibiotic exposure. Penicillin with extended spectrum (365 of 661 antibiotic prescriptions, 52.6%) and cephalosporins (12.0%) were the most frequently prescribed antibiotics. One fifth of antibiotics were prescribed for respiratory tract infections and bronchiolitis. CONCLUSION: Australian infants in this large population-based study are exposed to considerably more antibiotics than the majority of their international counterparts. Interventions aimed at addressing avoidable prescribing by medical practitioners and modifiable risk factors associated with antibiotic exposure may reduce antibiotic use.
-
ItemEmpiric antibiotic regimens for neonatal sepsis in Australian and New Zealand neonatal intensive care units(WILEY, 2017-07)AIM: Neonatal sepsis remains an important cause of morbidity and mortality, and requires prompt empiric treatment. However, only a minority of babies who receive antibiotics for suspected sepsis have an infection. Antimicrobial exposure in infancy has important short- and long-term consequences. There is no consensus regarding empirical antimicrobial regimens. METHODS: The study included a survey of empiric antimicrobial regimens in all tertiary neonatal intensive care units in Australia and New Zealand in 2013-2014. RESULTS: All 27 units responded. For early-onset sepsis, all units used a combination of gentamicin with either penicillin or ampicillin. For late-onset sepsis, the frequency of units using empiric vancomycin (41%) versus empiric flucloxacillin (48%) was similar. Gestational age or the presence of a central venous catheter had little influence on using vancomycin instead of flucloxacillin. For late-onset sepsis with meningitis there was marked variation in antimicrobial combinations, with 15 different regimens described. A total of 93% used a cefotaxime-based regimen, either as monotherapy (22%) or combined with a second (22%) or third (48%) agent. For suspected necrotising enterocolitis, 89% used an aminoglycoside, metronidazole and a penicillin. Historical outbreaks of multi-resistant organisms exerted long-term influence over regimen choice. CONCLUSIONS: There was limited use of broad-spectrum agents such as carbapenems or third-generation cephalosporins. In this region with low methicillin-resistant Staphylococcus aureus prevalence, empiric vancomycin use was common, selected for activity against coagulase-negative staphylococci. Empiric vancomycin is rarely necessary because coagulase-negative staphylococci are often contaminants and sepsis is rarely fulminant, occurring almost exclusively in extremely low birthweight infants. Implementation of appropriate, local antimicrobial policies is crucial to minimise antimicrobial exposure in this vulnerable population and halt the development of antimicrobial resistance.
-
ItemProbiotics and antimicrobial protein and peptide levels in preterm infants(WILEY, 2017-11)AIM: To characterise the secreted and inducible antimicrobial protein and peptide (APP) levels in a prospective cohort of preterm infants (<30 weeks gestational age) with or without Bifidobacterium breve M16V supplementation during the first month of life. METHODS: We analysed serial biosamples of infants who did (n = 13) or did not receive (n = 62) B. breve (3 × 109 cfu/day). Peripheral blood was obtained on days 1, 14 and 28, and infant stool prior to commencement of probiotic supplementation and on day 21. Levels of APP (bactericidal/permeability inducing protein (BPI), beta defensins 1 and 2, lactoferrin, human cathelicidin, secretory phospholipase A2) in plasma and stool were determined. Further, we characterised induced APP levels in whole blood cultured with live S. epidermidis or with agonists of Toll-like receptors 2/6 and 4. RESULTS: Stool, plasma and stimulated blood APP levels changed significantly during the first month of life. Supplementation with B. breve did not affect basal or stimulated APP levels except for a transient increase in inducible BPI. CONCLUSION: Supplementation with B. breve does not appear to act via modulation of systemic or enteric APP expression in preterm infants although small effects cannot be excluded. Further work with other probiotic preparations is warranted.
-
ItemVitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study(WILEY, 2017-08)BACKGROUND: Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. OBJECTIVE: To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. METHODS: In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D3 (25(OH)D3 ) levels among infants with food allergy vs a random subcohort (n = 274). The primary exposures were VDI (25(OH)D3 <50 nM) at birth and 6 months of age. Ambient UVR and time in the sun were combined to estimate UVR exposure dose. IgE-mediated food allergy status at 1 year was determined by formal challenge. Binomial regression was used to examine associations between VDI, UVR exposure dose and food allergy and investigate potential confounding. RESULTS: Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. CONCLUSIONS: There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required.
-
ItemThe association between higher maternal pre-pregnancy body mass index and increased birth weight, adiposity and inflammation in the newborn(WILEY, 2018-01)BACKGROUND: Excess adiposity and adiposity-related inflammation are known risk factors for cardiovascular disease in adults; however, little is known regarding the determinants of adiposity-related inflammation at birth. OBJECTIVES: The aim of this study was to investigate the association between maternal pre-pregnancy BMI and newborn adiposity and inflammation. METHODS: Paired maternal (28-week gestation) and infant (umbilical cord) blood samples were collected from a population-derived birth cohort (Barwon Infant Study, n = 1074). Data on maternal comorbidities and infant birth anthropomorphic measures were compiled, and infant aortic intima-media thickness was measured by trans-abdominal ultrasound. In a selected subgroup of term infants (n = 161), matched maternal and cord lipids, high-sensitivity C-reactive protein (hsCRP) and maternal soluble CD14 were measured. Analysis was completed by using pairwise correlation and linear regression. Because of their non-normal distribution, pathology blood measures were log transformed prior to analysis. RESULTS: Maternal pre-pregnancy BMI was positively associated with increased birth weight (mean difference 17.8 g per kg m-2 , 95% CI 6.6 to 28.9; p = 0.002), newborn mean skin-fold thickness (mean difference 0.1 mm per kg m-2 , 95% CI 0.0 to 0.1; p < 0.001) and cord blood hsCRP (mean difference of 4.2% increase in hsCRP per kg m-2 increase in pre-pregnancy BMI, 95% CI 0.6 to 7.7%, p = 0.02), but not cord blood soluble CD14. Inclusion of maternal hsCRP as a covariate attenuated the associations between pre-pregnancy BMI and both newborn skin-fold thickness and cord blood hsCRP. CONCLUSION: Higher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy.
-
ItemInflammation, lipids and aortic intima-media thickness in newborns following chorioamnionitis(WILEY, 2016-07)AIM: This study investigated whether chorioamnionitis was associated with increased inflammation, dyslipidaemia and adverse cardiovascular phenotypes in the immediate postnatal period. METHODS: This prospective case-control study included preterm infants (30(+0) -35(+6) weeks gestational age, GA) whose mothers did not have pregnancy-related conditions that may influence outcomes. Chorioamnionitis was diagnosed by placental histology, and infants were divided retrospectively into cases (chorioamnionitis-exposed) and controls (unexposed). Serum high-sensitivity C-reactive protein (hsCRP), lipid profile, far-wall abdominal aortic intima-media thickness (aIMT) and blood pressure (BP) were measured in the first week of life. RESULTS: There were 20 (16 male, mean GA 32.4 weeks) cases and 31 (12 male, mean GA 32.6 weeks) controls. Histological chorioamnionitis was associated with a significant increase in hsCRP and a non-significant trend towards an adverse lipid profile. There was no evidence of differences in aIMT or BP. CONCLUSION: Preterm infants exposed to chorioamnionitis have greater postnatal inflammation. There were no early postnatal differences in aIMT or BP. The inflammatory stimulus of chorioamnionitis late in gestation may be of insufficient intensity and duration to result in immediate postnatal alterations to arterial structure. Cardiovascular follow-up of infants exposed to chorioamnionitis may identify differential risk trajectories and subsequent inflammatory responses.
-
ItemKawasaki disease and cardiovascular risk: a comprehensive review of subclinical vascular changes in the longer term(WILEY, 2016-07)UNLABELLED: Studies of subclinical vascular changes post-Kawasaki disease indicate that, in general, individuals with a history of coronary artery aneurysms have increased carotid intima-media thickness, evidence of endothelial dysfunction, and increased arterial stiffness, possibly indicative of heightened cardiovascular risk. The results are less consistent for low-risk groups. CONCLUSION: Until data are available from larger prospective studies, it is prudent to advise families of individuals with a history of Kawasaki disease to minimise traditional modifiable cardiovascular risk factors.
-
ItemTelomere length and lung function in a population-based cohort of children and mid-life adults(WILEY, 2019-12)OBJECTIVE: Telomere length is associated with poorer lung health in older adults, possibly from cumulative risk factor exposure, but data are lacking in pediatric and population-based cohorts. We examined associations of telomere length with lung function in children and mid-life adults. METHODS: Data were drawn from a population-based cross-sectional study of 11 to 12 year-olds and mid-life adults. Lung function was assessed by spirometric FEV1 , FVC, FEV 1 /FVC ratio, and MMEF 25-75 . Telomere length was measured by quantitative polymerase chain reaction from blood and expressed as the amount of telomeric genomic DNA to the beta-globin gene (T/S ratio). Associations of telomere length with spirometric parameters were tested by linear and logistic regression models, adjusting for potential confounders of sex, age, body mass index, socioeconomic position, physical activity, inflammation, asthma, pubertal status, and smoking. RESULTS: Mean T/S ratio was 1.09 (n = 1206; SD 0.55) in children and 0.81 (n = 1343; SD 0.38) in adults. In adults, for every additional unit in T/S ratio, FEV 1 /FVC and MMEF 25-75 z-scores were higher (β 0.21 [95% confidence interval, CI; 0.06-0.36] and 0.23 [95% CI; 0.08-0.38], respectively), and the likelihood of being in the lowest quartile for FEV 1 /FVC and MMEF 25-75 z-scores was lower (odds ratios 0.59 [95% CI, 0.39-0.89] and 0.64 [95% CI, 0.41-0.99], respectively). No evidence of association was seen for adult FEV 1 or FVC, or any childhood spirometric index after adjustments. CONCLUSION: Shorter telomere length showed moderate associations with poorer airflow parameters, but not vital capacity (lung volume) in mid-life adults. However, there was no convincing evidence of associations in children.
-
ItemAssociations of retinal microvascular caliber with intermediate phenotypes of large arterial function and structure: A systematic review and meta-analysis(WILEY, 2019-10)OBJECTIVE: Intermediate phenotypes of microcirculation (retinal microvascular caliber) are associated with cardiovascular (CV) risk factors and independently predict CV events. However, the effect of microcirculation variation on the vascular system is unclear. We conducted a systematic review and meta-analysis of observational studies to quantify associations of retinal microvascular caliber (arteriolar, venular caliber, arteriole-to-venule ratio) and preclinical CV measures (large arterial function and structure). METHODS: We identified studies in MEDLINE, EMBASE, and PubMed (1946 to March 2018) studying (a) general population samples and (b) patients with cardiometabolic disease. Study-specific correlation estimates were combined into meta-analysis where possible. RESULTS: Of 1294 studies identified, 26 met inclusion criteria (general population 16, patients 10), of which five studies were included in meta-analysis. Most studied middle-aged adults cross-sectionally, with one childhood study. Large arterial function and structure were predominantly assessed by pulse wave velocity and carotid intima-media thickness, respectively. Only arteriolar caliber was consistently associated with arterial function and structure, with stronger associations observed in cardiometabolic patients. Narrower (worse) arteriolar caliber was associated with faster (poorer) pulse wave velocity (correlation coefficient (r) -0.17, 95% CI -0.25 to -0.10) and greater (poorer) intima-media thickness (r -0.05, 95%CI -0.09 to -0.02) across all adult participants. CONCLUSIONS: Retinal arteriolar, but not venular caliber, was modestly associated with large arterial function and weakly associated with large arterial structure, with stronger evidence in patients with cardiometabolic disease. This suggests that preclinical changes in large arteries and the microcirculation have some shared but mainly unique pathways to associate with cardiovascular disease.
-
ItemNaive regulatory T cells in infancy: Associations with perinatal factors and development of food allergy(WILEY, 2019-09)BACKGROUND: In previous studies, deficits in regulatory T-cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy. METHODS: In a birth cohort (n = 1074), the proportion of nTreg in the CD4+ T-cell compartment was measured by flow cytometry at birth (n = 463), 6 (n = 600) and 12 (n = 675) months. IgE-mediated food allergy was determined by food challenge at 1 year. Associations between perinatal factors (gestation, labour, sex, birth size), nTreg at each time point and food allergy at 1 year were examined by linear regression. RESULTS: A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg. Infants that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy. CONCLUSION: The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy.