INFANT Research Centre - Masters by Research Theses
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Item The NEST study: NICOM vs ECHO in the screening of transient hypertrophic obstructive cardiomyopathy (HOCUM)(University College Cork, 2023) Finn, Bryan Padraig; Ó Tuathaigh, Colm; Dempsey, Eugene M.; University College CorkBackground: Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy. An increasing number of infants are exposed to hyperglycaemia antenatally with the national prevalence estimated at 10.1-12.4%. Transient HOCUM (Hypertrophic Obstructive Cardiomyopathy) as well as interatrial/interventricular communications remain the most common cardiac sequelae for such infants. In particular, transient HOCUM has a broad estimated international incidence of 13-44%. The current standard of care for infants born to mothers with GDM (Gestational Diabetes Mellitus) is unchanged from routine care, consisting of a bedside newborn examination. A further echocardiogram is subsequently performed if clinically indicated as a key investigation for the detection of congenital heart disease. There has been a rising interest in NICOM (Non-invasive Cardiac Output Monitoring), a range of novel non-invasive measurements of cardiac output and left ventricular outflow using an array of techniques from electrical bioimpedance to transthoracic bioreactance. The appeal is that these investigations can be carried out at the patient’s bedside without a trained ECHO (Echocardiogram) technician. Aim: Our primary aim was to assess the ability of transthoracic bioreactance (a novel method of cardiac output measurement) in detecting left ventricular outflow tract obstruction in a high-risk group. Echocardiography at present is the most commonly used tool in the detection of such cases, whereby left ventricular outflow tract obstruction is secondary to transient hypertrophic obstructive cardiomyopathy (HOCUM) for infants born to mothers with GDM. We hoped to determine if bioreactance (a NICOM branch technology) could be used as a screening tool when compared with the best available standard of echocardiography. Methods: A single centre prospective observational cohort study was conducted. Our primary objective was to compare bioreactance using the NICOM TM device against the most commonly used method of obtaining LVO measurements: echocardiography in infants born to mothers with GDM. Our goal was to ascertain if NICOM could be used as a screening tool to detect those infants at risk of symptomatic transient HOCUM with LVOTO (left ventricular outflow tract obstruction). For the purposes of secondary objectives, maternal demographic characteristics including BMI (Body Mass Index), maternal age, maternal HbA1C (glycosylated haemoglobin) and method of diabetes control were collected from the electronic healthcare record. Infant demographic and clinical variables collected included infant gestation, anthropomorphic measurements, newborn clinical examination findings and if the infant was admitted to the neonatal unit (indication and treatment received). The data analysis strategy employed was primarily using Pearson’s correlation co-efficient to determine if bioreactance had comparable efficacy to echocardiography in the detection of reduced left ventricular outflow as expected in clinically significant transient HOCUM. Preliminary statistics revealed for Pearson’s correlation- a sample size of 29 patients was required to detect a large correlation (Cohen’s r = 0.5)). This was further assessed using a Bland Altman plot. Otherwise, univariate analysis of the transient HOCUM cohort was carried out using Chi Square tests for categorical variables and independent T-tests for continuous variables. Results: Fifty infants underwent echocardiography while 28/50 of these infants were paired with a NICOM assessment (four echocardiogram data sets lost due to HSE cyberattack). 4/46 patients (8.7%) were noted to have a z-score of >2 for both the interventricular septal wall thickness and left posterior ventricular wall in diastole (LVPWd) consistent with a diagnosis of transient HOCUM with LVOTO. 26 out of 46 infants born to mothers with diabetes had significant thickening (Z-score >2) of either the interventricular septum or the left posterior ventricular wall. Regarding congenital heart defects, VSDs (ventricular septal defects) were found in 8.7% (4/46) of the study population with one patient found to have a >3mm ASD secundum. The incidence of transient HOCUM was not associated with the degree of maternal glycaemic control, maternal BMI or the method of diabetes control (all P > 0.05). Bioreactance LVO measurements poorly correlated with ECHO LVO values (r(25)= 0.2, p=- 0.31) with an ambiguous agreement on Bland Altman analysis. Conclusion: The incidence of transient HOCUM in our cohort (8.7%) was lower than previous studies -13-44%. Transthoracic bioreactance does not appear to be an effective screening tool for transient HOCUM with LVOTO in this high-risk cohort of patients. This is on the basis of a poor Pearson correlation with ECHO derived LVO values and the wide limits of agreement found with the Bland Altman plot. Infants born to mothers with GDM would not benefit from routine echocardiography screening beyond the current standard of care. This is owing to our findings that all cases of clinically relevant congenital heart disease in our cohort would have been detected with the current standard of care- a newborn bedside examination followed by a targeted ECHO as clinically indicated.Item Single dose challenges in the diagnosis and management of cow's milk allergy in infants(University College Cork, 2021-06-28) d'Art, Yvonne; Hourihane, Jonathan O'B.; Gibson, Louise; Byrne, Aideen; National Children's Research CentreBackground: Cows milk protein allergy (CMPA) is one of the most common food allergies in infancy. While it usually resolves slowly over time in most cases, it significantly disrupts family life and compromises affected childrens’ nutrition and growth. Parents often display significant anxiety about this condition and we speculated if this anxiety predates or develops in response to the onset of CMPA in their child. Single dose challenges are a new method of assessing dose reactivity in food allergic children. We recruited children referred for evaluation of CMPA to a randomised, controlled trial of single dose exposure to cows milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED05, before implementation of graded exposure to CM (using the 12 step IMAP Milk Tolerance Induction Ladder) at home. Methods: 60 infants were recruited from referrals to 2 tertiary allergy centres and 1 secondary level allergy clinic. Inclusion criteria were age <12 months, a convincing CM allergic reaction <2 months before assessment and positive skin prick test (SPT) to milk +/- raised SpIgE to milk. Children were randomised 2:1 to a single dose of the ED05 for CM - (0.5mg milk protein) given as liquid CM (0.015mls) and observed for 2 hours post ingestion - or to no dose. Results: 60 patients were recruited, 57 (95%) were followed to 6 months, 3 intervention subjects were lost to follow up. By 6 months 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p=0.048). By 6 months 11/37 (30%) intervention subjects reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). 12 months post randomisation 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above.However 23/36(64%) of the intervention group were at step 12 compared to 7/19(37%) of the control group. Maternal state and trait anxiety were significantly associated with their infants’ response/progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion Using the 12 step IMAP milk ladder accelerates natural tolerance induction in infants under 12 months with CMPA. A supervised single dose at the ED05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards tolerance but preexisting high levels of maternal anxiety are associated with poorer progress.