2011-05-30

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An Evidence-Based View on Hyperbilirubinemia: Nice to know or Must-know?

Peter H. Dijk

Department of Neonatology, Beatrix Children’s Hospital, University Medical Center Groningen, the Netherlands.

Cohrane Reviews

Conclusions phenobarbital no evidence on efficacy and safety single vs double vol ET insufficient data to switch to single

volume ET metalloporphyrines ↓TSB, longterm effects?

insufficient data intravenous nutrition no evidence on efficacy and safety immunoglobulines ↓TSB and need ET

insufficient data fibreoptic PT safe, less effective CPT in term

as effective in preterm infants. FOPT+CPT > CPT alone

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Other Reviews Efficacy of treatments Evans 2007 PT beneficial, ET likely beneficial, albumin and mesoporphyrins: unknown Usefulness of bilirubin-albumin ratio Hulzebos 2008 correlation BA ratio – ND outcome vs TSB – ND outcome Stategies to prevent hyperbilirubineamia Trikalinos and Ip 2009 combination of risk factor + early bilirubin measurement Nomograms of TcB De Luca 2009 rate of rise formula Phenobarbitone in pretems Chavla 2010 beneficial in resource restricted, reduce TSB, PT, ET Genetic polymorphism Long 2011 UGT1A1 211G>A associated in Asians (OR 2.5), not Caucasians

Reviews & guidelines AHRQ review 2002 AAP guideline 2004 5 questions -  relation bilirubin and neurodevelopmental outcome -  influence other variables / riskfactors -  efficacy of treatment -  accuracy of prediction strategies -  accuracy of transcutaneous bilirubin measurement MCC-WCH review NICE guideline 2010 6 questions -  riskfactors hyperbilirubinaemia + adverse outcome -  accuracy of prediction strategies (incl TcB) -  accuracy of recognising methods (incl TcB) -  diagnostic tests -  efficacy of treatments, monitoring, discharge and follow-up -  information given to parents

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National Cohorts Conclusions Incidence kernicterus: 1 - 2.5 per 100.000 Incidence severe hyperbilirubinemia 4 – 143 per 100.000 TSB>425 or > ET-limit Causes System failures of complex health care organisations Shortcomings in clinical and service provision

Summary Effective LED PT double PT overhead PT extra fluid Not (more) effective Reflecting material Triple PT Underneath (vs overhead) Turning the infants (vs supine)

RCT’s Phototherapy RCT’s Pharmacology

Summary Effective Prebiotics Clofibrates Pre-exchange albumin Yinzhiuhang-Taihuang Not effective Gemfibrozil

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Ongoing RCT’s

Ongoing trials in Trial registries

Breastfeeding support

Formula feeding

Transcutaneous bilirubin measurements

Carboxy hemoglobine measurements

Pharmacological trials

LED phototherapy

Information technology

Bilirubin:albumin ratio

Ongoing RCT’s BARTrial

Cost-effectiveness trial

Reducing bilirubin induced neurological dysfunction by using bilirubin:albumin ratio together with TSB vs TSB only as indicator for treatment of hyperbilirubinemia in preterm infants

P Preterm infants < 32 wks PMA

I BA ratio + TSB

C TSB only

O neurodevelopmental outcome 2 yrs (B3)

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Conclusions Kernicterus still exists World-wide prevention relatively easily causes developed countries: system failure of complex health care org’s screening Risk factor assessment and early measurement of bilirubin TcB reduces need for blood sampling therapy phototherapy pharmacological adjuvant therapies

Conclusions Research Recommendations Risk factors vulnerability bilirubin neurotoxicity Genetics – polymorphisms hyperbilirubinemia and vulnerability Relation breastfeeding and hyperbilirubinemia Prevention and early detection strategies Root causes of system-failure in timely diagnosis Root causes of sytem-failure in treatment Pharmacological trials Implementation strategies for guidelines Clear recommendations Simple format – easy to find Easy to use in daily clinical practice

2011-05-30

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Guideline website

Website Babyzietgeel.nl 11th commandment: information communication between health-care Workers when a baby is transferred from home to hospital or v.v. Chronological order of the recommendations for each professional 5W’s: Who does What to Whom, When, and in What way Tools: tables, graphs and summary boxes and supplements PT, ET, IVIG, and using transcutaneous bilimeters Information for parents Background information Teaching materials Indicators for Quality of Care - audit

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Online and printable bili-graphs

treatment thresholds EHD in press

Conclusions Implementation strategies of guidelines Rephrase into clear recommendations (5W’s) Reorganize into logical order Summarize per health care worker Provide handy tools and protocols Spread the news Summary cards Teaching materials for all health care workers involved