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Table 2 Levels of intervention and suggested tools for managing neonatal hyperbilirubinaemia in low and middle-income countries

From: Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings

Proposed tasks or tests [Applicable level of care]* Suggested tools and facilities
Primary prevention  
• Education of existing and expectant mothers, families and health care providers on [P, S & T]: • Educational materials including posters and audio-visual aids where available, pictures and/or video clips of infant survivors of BIND and/or Kernicterus. This material should include signs of both early and late ABE/BIND and potential long-term consequences of ABE/BIND for both the community and the health care providers. [P, S & T]
 o The transient physiologic course but with potential to increase to harmful levels and it's variability from baby to baby
 o The avoidance of haemolytic substances (including camphor/naphthalene balls, menthol-containing powder, creams and balms, e.g. Wintergreen oil).
 o The benefits of early detection accompanied by timely and appropriate treatment in health facilities adequately-equipped for newborn care. Access to laboratory appropriately resourced for clinical investigations. [S & T]
 o Discouraging traditional therapies as well as indiscriminate use of self-prescribed medications e.g. ampicillin-cloxacillin.  
 o Recognition of acute bilirubin encephalopathy/Bilirubin-Induced Neurologic Dysfunction (BIND)
 o The value of “clean birth” to prevent or minimize the risk of infection (sepsis)
• Referral to secondary or tertiary centers of all preterm babies (<35 weeks gestation) and surveillance for full-term infants with history of medically-treated jaundice in a sibling presenting at primary health centers. [P]
• Promotion and support for successful breastfeeding. [P, S & T]
• Screening of expectant mothers for the risk of blood group incompatibilities using routine ABO & Rh with counseling on the importance of Rh immunoglobulin ensuring availability when indicated. [P, S & T]
• Judicious use of oxytocin during labor. [S & T]
• Identification of babies with extensive bruises, cephalhaematomas and at risk for concealed haematomas e.g. those from difficult deliveries. [P, S & T]
• Request blood test to rule out Glucose-6-phosphate dehydrogenase (G6PD) deficiency in high-risk populations. [S & T]
• Early phototherapy for infants with hemolytic diseases. [S & T]
Early detection, diagnosis and monitoring  
• Routine examination of all newborns within 24 hours of birth and the next 48 hours for possible jaundice. [P, S & T] • Well-lit examination room or nursery with natural daylight (minimum). [P, S & T]
• If jaundice is suspected, examine infant naked in a well-lit room or, preferably in natural daylight near a window guided by Kramer’s chart (Additional file 3: Figure S1). Recognize that estimation of the degree of hyperbilirubinaemia based on visual signs of jaundice can lead to errors, particularly in darkly pigmented infants. Blanching of the gum may be more reliable and helpful in dark skinned babies. [P, S & T] • Transcutaneous (TcB) Bilirubinometer e.g. JM103® or Bilicheck® (minimum) or Icterometer. [P, S & T]
• Rapid micro device for total plasma/serum bilirubin (TSB) (minimum). [S & T]
• Bilirubinometer for total serum & direct bilirubin measurement (minimum). [S & T]
• If jaundice is visible, measure the total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) level. TcB values above 12 mg/dl (205 μmol/L) should be cross-checked where possible with TSB measurement. [P, S & T] • Access to laboratory facilities for: [S & T]
 o Blood group, Rh, G6PD tests (minimum)
 o Components of sepsis screen such as Complete Blood Count, Blood/Urine/CSF cultures, CRP and/or other rapid screening tests
• Establish if infant has early signs of acute bilirubin encephalopathy (ABE) or qualifies as high risk including possible hemolytic diseases, hypothermia, hypoglycemia, or sepsis (see Algorithm in Figure 1). [P, S & T]  o Metabolic screening e.g. hypothyroidism, galactosaemia when indicated.
• Follow the Algorithm and Table 3 for actionable levels. [P, S & T]
• Ensure follow-up of infants discharged before 48 hours after delivery especially those with established risk factors within 1–2 days of discharge (take advantage of BCG visit and any other times infants <2 weeks are seen). [P, S & T]
• Follow the Algorithm and Table 3 for actionable levels after country specific adaptations. [S & T] • Effective Phototherapy Units [S & T]
• When indicated (particularly, in the presence of isoimmune haemolytic diseases), ensure early treatment of newborns with intensive phototherapy to minimize the need for exchange transfusion. [S & T]  o Special Blue-light Phototherapy Unit (ideal)
 o Light emitting diodes (LED) Phototherapy Unit (ideal)
• Ensure that the irradiance levels of phototherapy units are periodically monitored and the recommended specifications strictly followed. [S & T]
 o Fluorescent white or blue bulbs (minimum)
• Be familiar with simple and inexpensive adjustments that can significantly improve the effectiveness of phototherapy devices. [S & T] • Irradiance Meters (spectro-radiometers) (ideal). [S & T]
• Access to blood bank with fresh (ideally less than 3 days old) whole blood for ET appropriately compatible with mother and baby (O and Rh specific). [S & T]
• Maximize irradiance by placing the units as close as possible without overheating the infants (usually 10–20 cm above the baby if using cool lights (unless specified otherwise by manufacturer), using reflecting materials on all sides of cots, exposing as much of the baby as possible (thereby maximizing spectral power [irradiance x size of irradiated area]); and change florescent tubes according to manufacturer’s recommendations if available or periodically (8–12 weeks) if unable to measure irradiance levels [S & T]
• Intravenous immunoglobulins (IVIG) may be useful when nearing ET but existing evidence is not conclusive. [T]
• Laboratory facilities for albumin [S & T]
• Ensure that the eyes are covered but keep the cover small to maximize surface available for PT. [P, S & T]  o Consider bilirubin-albumin ratio in addition to but not in lieu of total bilirubin level as a factor in determining the need for an exchange transfusion.
• Ensure that male genitals are covered (controversial) unless for infants nearing exchange transfusion level. [P, S & T]
• Ensure that babies are placed in cots not incubators when under phototherapy unless they are hypothermic. [S & T]
• Ensure that blood samples for relevant investigations are collected and refrigerated before initiating exchange transfusion and any blood samples are protected from light including the PT light. [S & T] • If available, consider the use of duly approved filtered sunlight phototherapy (FS-PT) in tropical settings with irregular electricity supply and lack of adequate or functional conventional phototherapy (CPT) units with careful and frequent monitoring of infants for temperature fluctuations. [ P & S]
• Ensure that an infant with clinical signs of moderate-severe ABE receives exchange transfusion promptly. Place the infant under the best phototherapy available while preparing for the exchange transfusion.[S & T]
• Ensure that the infant remains adequately hydrated and is breastfeeding well/feeding well. [P, S & T]
• Avoid drugs that compete for albumin binding such as sulfonamides, ceftriaxone, and acetylsalicylic acid. [S & T]
Follow-up evaluation  
• Assessment of non-jaundiced infants on days 3 and 5. [P, S & T] • Tools for age-appropriate developmental assessment. [S & T]
• Assessment of jaundiced infants regularly in the first 7–10 days or until jaundice is clearly resolved. [P, S & T]
• Automated Otoacoustic Emissions (AOAE). [S & T]
• Educate parents on the need for a follow-up neuro-developmental assessment of all infants treated for severe hyperbilirubinaemia with intensive phototherapy or exchange transfusion or with a history of such treatment at age 3–6 months. [P, S & T] • Automated Auditory Brainstem Response (AABR). [S & T]
• Access to diagnostic evaluation with Auditory Brainstem Response (ABR) (ideal). [T]
• Ensure that, at the minimum, such developmental assessment includes auditory brainstem response audiometry, language processing/language development and clinical evaluation of abnormalities of tone, posture and movements for infants with signs of ABE/BIND, who had exchange transfusion and those with a bilirubin level of >20 mg/dL. [S & T] • Consider Magnetic Resonance Imaging (MRI) for early detection of potential neurotoxicity if readily available, can be done without sedation and does not delay treatment. [T]
• Disseminate information on the local providers of age-appropriate developmental evaluation of infants and young children to the affected parents on discharge or during any subsequent clinical consultations. [S & T]  
  1. *Level of care where task/test should be available routinely: Primary/Community Health Center [P], Secondary/District Hospital [S], Tertiary/Children’s’ Hospital [T]. For a comprehensive list of essential infrastructural and human resources typically required for secondary/district hospitals see: UNICEF India. Toolkit for Setting up of Special Care Units, Stabilization Units and Newborn Care Units. New Delhi: UNICEF India, 2009.
  2. ➢ → Conventional Phototherapy (CPT): Phototherapy in which intensity of blue light (400–520 nm) with a peak wavelength of 450 ± 20 nm not less than 8 μW/cm2/nm is applied to the greatest possible surface area of the infant. The light sources are usually special blue fluorescent lamps, compact florescent lamps (CFL) or halogen spotlights. If none of these are available, ordinary commercial white/daylight fluorescent lights should be considered, but brought as close as possible (10-20 cm) to the baby without overheating.
  3. ➢ → Light-emitting diode Phototherapy (LED-PT): Phototherapy devices which emit most of their light in the 450–470 nm spectrum. This range corresponds to the peak absorption wavelength (458 nm) at which bilirubin is broken down. Blue LEDs are power efficient, portable devices with low heat production so that they can be placed very close to the skin of the infants without any apparent untoward effects.
  4. ➢ → Intensive Phototherapy (IPT): Phototherapy in which a high intensity of blue light (400–520 nm) ≥30 μW/cm2/nm is applied to the greatest possible surface area of the infant. In usual clinical situations, this will require special high-intensity fluorescent tubes, or CPT lamps placed approximately 30 cm (10 cm for cool blue light) above the infant, who can be nursed in a bassinet.
  5. ➢ → Filtered Sunlight Phototherapy (FS-PT): Treatment with specially filtered sunlight using custom pre-tested window-tinting films that protect against potentially harmful ultra-violet and infra-red rays.