Neonatal phototherapy A current perspective SC Peirce, Cardiff and Vale NHS Trust

Neonatal jaundice • Bilirubin • yellow pigment, by-product of breakdown of RBCs • conjugated in liver and excreted in bile • unconjugated bilirubin passes blood-brain barrier & is neurotoxic

• Neonatal transition period - imbalance • fetal RBCs are short lived • neonatal liver often too immature to conjugate bilirubin • accumulation of bilirubin in blood = “physiological hyperbilirubinemia” • yellow discolouration of skin = “neonatal jaundice” (>5-7 mg/dL)

Neonatal jaundice • Physiological hyperbilirubinemia (no disease) • • • • •

45-70% of full-term neonates bilirubin levels peak 2-4days after birth usually resolves without treatment peaks are later and higher in near-term infants prevalence is ~80% in pre-term infants

• Pathological hyperbilirubinemia • breast milk jaundice • blood group incompatibility (ABO, haemolysis) • Gilbert’s & Crigler-Najjar syndromes (rare)

Neonatal jaundice • Complications • acute bilirubin encephalopathy (reversible) • kernicterus (irreversible - hearing, cerebral palsy, tooth enamel)

• Treatment • monitor levels, ensure adequate hydration & feeding • phototherapy (~15 mg/dL) • exchange transfusion for severe cases (~20-25 mg/dL), 3-4 per 1000 mortality, 5-10% permanent cardiovascular sequelae

Photobiology 1950’s • Sister notices blanching of yellow skin pigment of infant left in sun • Cremer et al notice photosensitivity of samples of serum bilirubin • Publish in vitro absorption spectrum for bilirubin; peaks around 450-460nm (blue) • Jaundiced infants given alternating15-20min exposures to direct sunlight

Photobiology Absorption curve and spectral distribution of destruction of serum bilirubin in vitro (Cremer et al, Lancet 1958)

Photobiology Unconjugated bilirubin

Oxidation

Configurational Structural isomerisation isomerisation (reversible) (irreversible) lumirubin

Photobiology • In vivo bilirubin is bound to albumin and the absorption spectrum shifts slightly towards green (450-475 nm) • Efficacy of phototherapy treatment depends on: • • • • • •

spectrum irradiance (source and distance) exposed surface area duration initial bilirubin concentration skin thickness and pigmentation (?)

Devices Source • fluorescent tubes (blue, ‘special blue’, white, combined) – output reduces over time, should be replaced at defined intervals • tungsten halogen bulb (filtered, unfiltered/white) - heat • metal halide bulb (white) - heat • LEDs (high intensity galium nitrate) – long-lasting, no heat

Devices Configuration • conventional (CPT) – overhead lamps, can be used with incubators, recommended treatment distance • bed systems – light source is below infant, no eye covering required, can be used with radiant warmers • fibre-optic – flexible pad against skin, finite treatment area, no eye covering required, nursing during treatment • combined / whole body / wrap-around – overhead and underneath, double phototherapy, intensive phototherapy

Devices

Devices – fluorescent CPT

Devices – bulb CPT

Metal halide

Halogen

Devices – LED

Devices – fibre-optic / bed

Devices – combined / wraparound

Devices - spectra 0.35

Ultraviolet Medela Overhead @ 25cm

0.30 Irradiance (mW/cm2/nm)

Medela BiliBed

0.25 Heraeus 800 @ 40cm

0.20

Draeger 4000 @ 30cm

0.15 0.10 0.05 0.00 350

400

450

500

550

Wavelength(nm)

Fluorescent tubes and metal halide (Heraeus)

600

Devices - spectra 0.07

Ultraviolet Micro-Lite @ 43cm

0.06

Irradiance (mW/cm2/nm)

Ohmeda Spot @ 62.5cm Ohmeda BiliBlanket

0.05

0.04

0.03

0.02

0.01

0 350

400

450

500

Wavelength (nm)

Halogen bulbs

550

600

Spectra – LED CPT Spectral Irradiance(mW.cm -2.nm-1)

0.09 0.08 0.07 0.06 0.05 0.04 0.03 0.02 0.01 0 350

400

450

500 Wavelength

550

600

Devices - irradiance Device

Irradiance (mW/cm2) >1mW/cm-2 400 to 550nm

Mediprema Cradle 360

5.56 5.78 5.25

Natus neoBLUE (high)

2.29

Medela BiliBed Ohmeda BiliBlanket Plus

Ohmeda Spotlight Hill-Rom Micro-Lite Medela Overhead Draeger 4000 Vickers 80 Draeger Heraeus 800

11.71 2.50 4.66 3.39 0.81 4.24

Area >700cm2

9 9 9 9 9 9 9 9

9

9

9

Use in NI or IRW

9 9 9 9 9

9 9 9 9 9 9 9

Clinical practice •

• • • •

No consensus of serum concentration for • start/finish phototherapy • complications • exchange transfusions FOPT not different to CPT for pre-term infants (size) Combined FOPT and CPT not more effective than CPT alone “Intensive phototherapy” > 30 μW/cm2/nm (AAP) Large exposed area for more effective treatment, but periodic turning and the removal of nappies doesn’t (nec.) improve results, ventral surface is approximately 30% of total BSA

Clinical practice • • • • • •

Intermittant therapy may be as effective as continuous therapy Green light as effective as blue light for comparable irradiances Requirement to monitor water losses and body temperature Departments have variety of equipment types and maintenance regimes BS EN 60601-2-50 allows for 25% variation from the manufacturer’s specified irradiance value No evidence of any long-term sequelae or harms from phototherapy

Side effects • • • • • • • •

Increased transepidermal water loss Unwanted heating Alterations in blood flow patterns (?) Restlessness (CPT) Potential retinal hazard Impaired parental bonding (?) Oxidative injury (?) – pre-term babies treated with riboflavin Nausea, headaches and vertigo reported in carers around blue light sources

Problems •

• • •

No standardisation! • no in vivo action spectrum • no measurement of dose • can’t compare manufacturers’ irradiance values – different spectra, bandwidths, radiometers, distances Papers compare devices, often don’t provide sufficient information (irradiance, spectra/bandwidth, distance) Measurements on devices generally only made on a single item Users/purchasers don’t understand difficulties of comparing irradiance claims

Skin reflectance - race

Skin reflectance - jaundice

Neonatal phototherapy • Pathology of neonatal jaundice/hyperbilirubinaemia • Photobiology of bilirubin • Current devices • Current practice/guidelines • Side effects • Problems