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A parallel evaluation of three novel screening methods for hyperbilirubinaemia in newborns cared for at home

Projectomschrijving

Onderzoek naar drie nieuwe screeningsmethoden voor geelzien bij pasgeborenen

Vraagstuk

Veel baby’s zien een beetje geel in de eerste levensweek. Een teveel aan bilirubine, de kleurstof die het geelzien veroorzaakt, kan gevaarlijk zijn en zelfs levenslange handicaps veroorzaken. Wij onderzoeken drie nieuwe benaderingen om geelzien beter te herkennen, waardoor het op tijd behandeld kan worden en complicaties kunnen worden voorkomen.

Onderzoek

Bij baby’s die in de eerste week thuis zijn, gaan verloskundigen een huidmeter en een smartphone app gebruiken om de gele kleur te meten. Wanneer baby’s te geel zijn, wordt er zoals normaal bloed geprikt om het bilirubine te meten. Nu gebeurt dat in een laboratorium, vaak in het ziekenhuis. Wij gaan kijken of we met een nieuw apparaatje het bilirubine ook gewoon thuis kunnen meten.

Verwachte uitkomst

Na dit onderzoek weten we of we met deze nieuwe methoden te gele baby’s beter én sneller kunnen herkennen, om zo hun gezondheid nog beter te beschermen. Dit onderzoek is een samenwerking van o.a. het Erasmus MC, het UMCG en eerstelijns verloskundigenpraktijken.

Meer over pre- en neonatale screening

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Samenvatting van de aanvraag

BACKGROUND AND OBJECTIVE Neonatal jaundice, caused by elevated circulating bilirubin levels, is a physiologic phenomenon. However, when bilirubin levels are very high and left untreated, bilirubin may pass the blood-brain barrier and cause permanent brain damage (kernicterus spectrum disorder; KSD). In current practice, visual inspection is used as a first-line screening tool to assess hyperbilirubinaemia, even though it is known to be unreliable. Although KSD is entirely preventable, this reliance on visual inspection causes significant diagnostic and therapeutic delay. Accordingly, bilirubin levels rise to levels sufficiently severe to cause KSD in a significant number of neonates each year, representing a severe failure of the current maternity care system. Novel screening methods for early detection of potentially severe neonatal hyperbilirubinaemia and impeding KSD are urgently needed. We will perform a parallel evaluation of three novel screening methods for hyperbilirubinaemia in the home setting: 1. transcutaneous bilirubinometry (TcB); 2. an mHealth app (Picterus®) and 3. a hand-held point-of-care device for quantifying total bilirubin in whole blood (Bilistick®). HYPOTHESIS We hypothesise that among well neonates cared for at home during day 2-8 of life: 1. Universal TcB screening will improve recognition of neonates having hyperbilirubinaemia requiring treatment compared to visual inspection, while decreasing the need for heel pricks to quantify bilirubin in blood in case of suspected hyperbilirubinaemia. 2. The Picterus® app correlates well with TcB and laboratory-based bilirubin (LBB)levels and use of the Picterus® app will improve recognition of neonates having hyperbilirubinaemia necessitating treatment compared to visual inspection, while decreasing the need for heel pricks to quantify LBB. 3. In neonates requiring bilirubin quantification in blood, Bilistick® will have similar total bilirubin readings compared to LBB quantification, while reducing the time-to-test result and the volume of blood needed to determine total bilirubin in blood. INTERVENTIONS We will study the effectiveness of three novel screening approaches in parallel: 1. TcB screening: a non-invasive method for estimating total bilirubin in blood. 2. Picterus® app: a smartphone app which screens for neonatal jaundice using a photograph taken by a smartphone. 3. Bilistick®: a commercially available point-of-care test for total bilirubin in whole blood (25 µl). The transcutaneous bilirubinometer and the Picterus® app will be applied in all participants in conjunction with visual inspection (usual care) during each visit of the midwife at home. Bilistick® will only be used when LBB quantification is indicated (i.e. based on visual jaundice and/or elevated TcB reading). OUTCOME MEASURES Primary outcomes are hyperbilirubinaemia requiring treatment and heel pricks to quantify total bilirubin. In addition, we will assess the diagnostic properties of the Picterus® app and Bilistick®, user-convenience of the three novel methods, and a number of other secondary outcomes. SAMPLE SIZE CALCULATION We aim to include 2,000 neonates, which will provide: 1. 92% power to show that neonates who are not sufficiently jaundiced to probe LBB quantification (based on visual inspection) but who do have an elevated TcB level (i.e. TcB >= (LBB phototherapy threshold – 50 µmol/L)), at least 20% will have hyperbilirubinaemia requiring treatment. 2. 77% power to show that TcB quantification can safely (risk <3%) rule out hyperbilirubinaemia requiring treatment among neonates who are visually jaundiced but who have a TcB level below the threshold for LBB quantification (i.e. TcB more than 50 µmol/L below the LBB phototherapy threshold). These neonates can be saved a heel prick in the future. ANALYSIS The primary analysis will involve linear mixed models with hyperbilirubinaemia requiring treatment and heel pricks as dependent variable, the different interventions as independent variables, and a random intercept for neonate, accommodating repeated evaluation of each neonate. Diagnostic properties of the three methods will furthermore be evaluated using 2x2 tables and Bland-Altman plots. User-convenience will be assessed using descriptive statistics and qualitative methods. A formal cost-effectiveness analysis will be performed from a societal perspective. TIME SCHEDULE We aim to start participant inclusion by January 2021 and finalise inclusion by December 2022. Analysis, dissemination, incorporation of findings in the national guideline, and planning of follow-on projects and grants are planned for 2023. This project addresses a highly pressing issue and has significant potential to improve recognition of potentially severe hyperbilirubinaemia – and through doing so reduce KSD – while decreasing the need for heel pricks, time-to-test result, and health care costs.

Kenmerken

Projectnummer:
543002011
Looptijd: 89%
Looptijd: 89 %
2020
2024
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
dr. J.V. Been MD PhD
Verantwoordelijke organisatie:
Erasmus Medisch Centrum